来源 生物谷
2005-11-4 20:24:26

夫妇相随－－记华裔美国科学院院士伉俪詹裕农和叶公杼

生物谷

     有这样一对夫妻，他们来自同一所大学，毕业后同时被美国加州理工学院录取，就读期间同时从物理系转到了生物系，并且在从助理教授，到副教授，再到教授的过程当中，他们也是巧合地同一年晋升，1984年，他们又一次同时被霍德华休斯医学院（HHMI）聘为研究员。他们就是来自旧金山加州大学的詹裕农(Yuh-Nung　Jan) 叶公杼(Lily　Yeh　Jan)夫妻。这一个又一个巧合好似浑然天成，但是1996他们同时当选为美国科学院院士却是来自妻子的坚持――1995年妻子叶公杼被评为美国科学院院士，但是因为丈夫未获提名而婉言拒绝了这一殊荣，直到次年詹裕农也获提名，这样又促成了他们 “巧合”的同时成为美国科学院院士。

 

詹裕农叶公杼俩夫妇主要的研究方向是钾离子通道和果蝇神经发育，1986年他们在世界上首次克隆出了一种钾离子通道Shaker基因，这一工作与2003年的诺贝尔化学奖主题吻合，许多科学家表示获奖名单中没有他们的名字真是种遗憾。虽然未获得诺贝尔奖，但是詹裕农和叶公杼的工作得到了许多人的肯定，并且从他们实验室中也走出了多位华人科学家，其中包括获得Science杂志“青年科学家奖”的时松海，哥伦比亚大学杨建，麻省理工学院的沈华智和中国科学院上海交叉学科研究中心主任饶毅等等。


<strong>Yuh Nung Jan</strong>, professor of physiology, neuroscience and developmental biology. Photo by David Powers.

在各大顶级期刊，比如Cell，Science，Nature，Neuron等杂志上，詹裕农和叶公杼发表了许多文章，今年就有8篇。10月7日新一期Cell杂志题为“Common Molecular Pathways Mediate Long-Term Potentiation of Synaptic Excitation and Slow Synaptic Inhibition”的文章是他们的研究新成果。这篇文章从神经突触入手，研究发现CA1锥形神经元信号通路也可以引起慢抑制性突触后电位（slow inhibitory postsynaptic current ，sIPSC）的长时程增益作用（long-term potentiation，LTP）。

   同时，他们夫妇二人培养了至少40名教授，分布于全美各大大学，同时在他们实验室中也出现一大批顶尖的科学新苗子，如时松海等。

最新Cell原文：Common Molecular Pathways Mediate Long-Term Potentiation of Synaptic Excitation and Slow Synaptic Inhibition
Cindy Shen Huang,1,2,5 Song-Hai Shi,1,5 Jernej Ule,4 Matteo Ruggiu,4 Laura A. Barker,3 Robert B. Darnell,4 Yuh Nung Jan,1 and Lily Yeh Jan1,*

 
科学家Lily Jan
科学家Lily Jan
科学家Yuh—Nung Jan
科学家Yuh—Nung Jan

信息

·专题：华人科学家
·北美杰出华人科学家（生物医药类）
·美国华人名教授巡礼
·他们的实验室网页：http://www.ucsf.edu/jan/

 

发表文章的目录：

Transmitter actions and synapses

  1. Jan, L.Y., and Siegelbaum, S.A. (2005). Signaling mechanisms. Curr. Opin. Neurobiol. 15:253-256.  

  2. Margeta-Mitrovic, M., Jan, Y.N.,. and Jan, L.Y. (2001).  Function of GB1 and GB2 subunits in G protein coupling of GABAB receptors. Proc. Natl. Acad. Sci USA 98:14649-14654.  [PDF]

  3. Margeta-Mitrovic, M., Jan, Y.N., and Jan, L.Y. (2001).  Ligand-induced signal transduction within heterodimeric GABAB receptor. Proc. Natl. Acad. Sci. USA 98:14643-14648.  [PDF]

  4. Jan, L.Y., and Stevens, C.F. (2000). Signalling mechanisms. A decade of signaling. Curr. Opin. Neurobiol. 10:625-630.  [PubMed]

  5. Margeta-Mitrovic, M., Mitrovic, I., Riley, R.C., Jan, L.Y., and Basbaum, A.I. (1999). Immunohistochemical localization of GABAB receptors in the rat central nervous system. J. Comp. Neurol. 405:299-321.  [PubMed]

  6. Zerangue, N., and Jan, L.Y. (1998). G-protein signaling: fine-tuning signaling kinetics.   Curr.Biol. 8:R313-R316.  [PubMed]

  7. Jan, L.Y., and Jan, Y.N. (1997).  Receptor-regulated ion channels.  Curr. Opin. Cell Biol. 9:155-160  [PubMed]

  8. Liu, H., Wang, H., Sheng, M., Jan, Y.N., Jan, L.Y., and Basbaum, A.I. (1994).  Evidence for presynaptic N-methyl-D-aspartate autoreceptors in the spinal cord dorsal horn.  Proc. Natl. Acad. Sci. USA 91:8383-8387.  [PDF]

  9. Sheng, M., Cummings, J., Roldan, L.A., Jan, Y.N. and Jan, L.Y. (1994).  Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.  Nature 368: 144-147.  [PubMed]

  10. Bowers, C., Jan, L.Y. and Jan, Y.N. (1986).  A substance P-like peptide in bullfrog autonomic nerve terminals-Anatomy, biochemistry and physiology.  Neuroscience 19:343-356.  [PubMed]

  11. Jan, L.Y., Papazian, D., Timpe, L., O'Farrell, P., and Jan, Y.N. (1985).  Application of Drosophila molecular genetics in the study of neural function-studies of the Shaker locus for a potassium channel.  Trends Neurosci. 8:2334-238.

  12. Jan, L.Y. and Jan, Y.N. (1982).  Peptidergic transmission in sympathetic ganglia of the frog.   J. Physiol. 327:219-246.  [PubMed]

  13. Jan, L.Y., Jan, Y.N. and Brownfield, M.S. (1980).  Peptidergic transmitters in synaptic boutons of sympathetic ganglia.  Nature 288:380-382.[PubMed]

  14. Jan, Y.N., Jan, L.Y. and Kuffler, S.W. (1980).  Further evidence for peptidergic transmission in sympathetic ganglia.  Proc. Natl. Acad. Sci. USA 77:5008-5012.  [PDF]

  15. Jan, Y.N., Jan, L.Y. and Kuffler, S.W. (1979).  A peptide as a possible transmitter in sympathetic ganglia of the frog.  Proc. Natl. Acad. Sci. USA 76:1501-1505.  [PDF]

  16. Heuser, J.E., Reese, T.S., Dennis, M.J., Jan, Y.N., Jan, L.Y. and Evans, L. (1979).   Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release.  J. Cell Biol. 81:275-300.

  17. Jan, Y.N. and Jan, L.Y. (1978).  Genetic dissection of short-term and long-term facilitation in Drosophila.  Proc. Natl. Acad. Sci. USA 75:515-519.  [PDF]

  18. Jan, L.Y. and Jan, Y.N. (1976).  L-glutamate as an excitatory transmitter at Drosophila larval neuromuscular junction.  J. Physiol. 262:215-236.  [PubMed]

  19. Jan, L.Y. and Jan, Y.N. (1976).  Properties of the larval neuromuscular junction in Drosophila melanogaster.  J. Physiol. 262:189-214.  [PubMed]

Voltage-gated potassium channels

  1. Lai, H.C., Grabe, M., Jan, Y.N., and Jan, L.Y. (2005). The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel. Neuron 47:395-406.  [PubMed]

  2. Ionescu-Zanetti, C., Shaw, R.M., Seo, J., Jan, Y.N., Jan, L.Y., and Lee, L.P. (2005). Mammalian electrophysiology on a microfluidic platform. Proc. Natl. Acad. Sci. U.S.A. 102:9112-9117.  [PubMed]

  3. Surti, T.S., and Jan, L.Y. (2005). A potassium channel, the M-channel, as a therapeutic target. Curr. Opin. Investig. Drugs 6:704-711.  [PubMed]

  4. Grabe, M., Lecar, H., Jan, Y.N., and Jan, L.Y. (2004). A quantitative assessment of models for voltage-dependent gating of ion channels. Proc. Natl. Acad. Sci. USA 101:17640-17645.  [PubMed]

  5. Gutman, G.A., Chandy, K.G., Adelman, J.P., Aiyar, J., Bayliss, D.A., Clapham, D.E., Covarriubias, M., Desir, G.V., Furuichi, K., Ganetzky, B., Garcia, M.L., Grissmer, S., Jan, L.Y., Karschin, A., Kim, D., Kuperschmidt, S., Kurachi, Y., Lazdunski, M., Lesage, F., Lester, H.A., McKinnon, D., Nichols, C.G., O'Kelly, I., Robbins, J., Robertson, G.A., Rudy, B., Sanguinetti. M,, Seino, S., Stuehmer, W., Tamkun, M.M., Vandenberg, C.A., Wei, A., Wulff, H., and Wymore, R.S. (2003). International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacol Rev. 55:583-586.  [PDF]

  6. Cohen, B., Grabe, M. and Jan, L.Y. (2003). Answers and questions from the KvAP Structures. Neuron 39:395-400.  [PubMed]

  7. Cooper, E.C., and Jan, L.Y. (2003). M-channels: neurological diseases, neuromodulation, and drug development. Arch. Neurol. 60:496-500.  [PubMed]

  8. Yi, B.A., Minor, D.L., Jr., Lin, Y.-F., Jan, Y.N., and Jan, L.Y. (2001).  Controlling potassium channel activities: interplay between the membrane and intracellular factors.  Proc. Natl. Acad. Sci. USA 98:11016-11023.  [PubMed]

  9. Cooper, E.C., Harrington, E., Jan, Y.N., and Jan, L.Y. (2001).  M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain.  J. Neurosci. 21:9529-9540.  [PDF]

  10. Minor Jr., D.L., Lin, Y.-F., Mobley, B.C., Avelar, A., Jan, Y.N., Jan, L.Y., and Berger, J.M. (2000).  The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.  Cell 102:657-670.  [PubMed]

  11. Yi, B.A., and Jan, L.Y. (2000). Taking apart the gating of voltage-gated K+ channels.  Neuron 27:423-425.  [PubMed]

  12. Cooper, E. C., Aldape, K. D., Abosch, A., Barbaro, N. M. Berger, M. S. Peacock, W. S. Jan, Y. N. and Jan, L. Y. (2000) Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.  Proc. Natl. Acad. Sci. USA 97: 4914-4919.  [PDF]

  13. Zerangue, N. Jan, Y. N. and Jan, L. Y. (2000) An artificial tetramerization domain restores efficient assembly of functional Shaker channels lacking T1.  Proc. Natl. Acad. Sci. USA 97:3591-3595.  [PDF]

  14. Cooper, E.C. and Jan, L.Y. (1999). Ion channel genes and human neurological disease: recent progress, prospects, and challenges.  Proc. Natl. Acad. Sci. USA 96:4759-4766.  [PDF]

  15. Cooper, E.C., Milroy, A., Jan, Y.N., Jan, L.Y. and Lowenstein, D.H. (1998).  Presynaptic localization of Kv1.4-containing A-type potassium channels near excitatory synapses in the hippocampus.  J. Neurosci. 18:955-974.  [PDF]

  16. Jan, L.Y. and Jan, Y.N. (1997).  Ways and means for left shifts in the MaxiK channel.  Proc. Natl. Acad. Sci. USA 94:13383-13385.  [PDF]

  17. Jan, L.Y. and Jan, Y.N. (1997).  Voltage-gated and inwardly rectifying potassium channels. J. Physiol. 505:267-282.  [PDF]

  18. Xu, J., Yu, W., Jan, Y.N., Jan, L.Y. and Li, M. (1995).  Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.  J. Biol. Chem. 270:24761-24768.  [PDF]

  19. Klumpp, D.J., Song, E.J., Ito, S., Sheng, M.H., Jan, L.Y. and Pinto, L.H. (1995).   The Shaker-like potassium channels of the mouse rod bipolar call and their contributions to the membrane current.  J. Neurosci. 15:5004-5013.  [PDF]

  20. Sheng, M., Tsaur, M-L, Jan, Y.N. and Jan, L.Y. (1994). Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain.  J. Neurosci. 14:2408-2417.  [PDF]

  21. Lopez, G., Jan, Y.N. and Jan, L.Y. (1994).  Evidence that the S6 segment of the Shaker voltage-gated K+ channel comprises part of the pore.  Nature 367: 179-182.  [PubMed]

  22. Slesinger, P.A., Jan, Y.N. and Jan, L.Y. (1993).  The S4-S5 loop contributes to the ion selective pore of potassium channels.  Neuron 11:739-749.  [PubMed]

  23. Sheng, M., Liao, J., Jan, Y.N. and Jan, L.Y. (1993). Presynaptic A-current based on heteromultimeric K+ channels detected in vivo.  Nature 365:72-75.  [PubMed]

  24. Li, M., Jan, Y.N. and Jan, L.Y. (1992). Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker K+ channel.  Science 257:1225-1230.  [PubMed]

  25. Sheng, M., Tsaur, M-L, Jan, Y.N. and Jan, L.Y. (1992).  Subcellular Segregation of Two A-type K+ Channel Proteins in Rat Central Neurons.  Neuron 9:271-284.  [PubMed]

  26. Tsaur, M.L.,Sheng, M., Lowenstein, D.H., Jan, Y.N. and Jan, L.Y. (1992).  Differential expression of K+ channel mRNAs in the rat brain and down regulation in the hippocampus following seizures.  Neuron 8:1055-1067.  [PubMed]

  27. Jan, L.Y. and Y.N. Jan. (1992).  Structural elements involved in specific K+ channel functions.  Annu. Rev. Physiol. 54:537-555.  [PubMed]

  28. Isacoff, E.Y., Jan, Y.N. and Jan, L.Y. (1991).  Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel.  Nature 353:86-90.  [PubMed]

  29. Lopez, G.A., Jan, Y.N. and Jan, L.Y. (1991).  Hydrophobic Substitution Mutations in the S4 Sequence Alter Voltage-Dependent Gating in Shaker K+ Channels.  Neuron 7:327-336.  [PubMed]

  30. Baldwin, T.B., Tsaur, M-L, Lopez, G.A., Jan, Y.N. and Jan, L.Y. (1991).  Characterization of a mammalian K+ channel cDNA for an inactivating voltage-sensitive K+ channel.  Neuron 7:471-483.  [PubMed]

  31. Papazian, D.M., Timpe, L.C., Jan, Y.N. and Jan, L.Y. (1991).  Alteration of voltage-dependence of Shaker K+ channel by mutations in the S4 sequence.  Nature 349:305-310.  [PubMed]

  32. Klaiber, K., Williams, N., Roberts, T.M., Papazian, D.M., Jan, L.Y. and Miller, C. (1990).  Functional expression of Shaker K+ channels in a baculovirus-infected insect cell line.  Neuron 5:211-216.  [PubMed]

  33. Isacoff, E., Jan, Y.N. and Jan, L.Y. (1990).  Evidence for the formation of heteromulteric potassium channels in Xenopus oocytes.  Nature 345: 530-534.  [PubMed]

  34. Schwarz, T.L., Papazian, D.M., Carretto, R.C., Jan, Y.N. and Jan, L.Y. (1990).   Immunological characterization of K+-channel components from the Shaker locus and the differential distribution of splicing variants in Drosophila.  Neuron 4:119-127.  [PubMed]

  35. Jan, L.Y. and Jan, Y.N. (1989). Voltage-sensitive ion channels. Cell 56:13-25.  [PubMed]

  36. Timpe, L.C., Jan, Y.N. and Jan, L.Y. (1988).  Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes.   Neuron 1:659-667.  [PubMed]

  37. Tempel, B.L, Jan, Y.N. and Jan, L.Y. (1988).  Cloning of a probable potassium channel from mouse brain.  Nature 332:837-839.  [PubMed]

  38. Timpe, L.C., Schwarz, T.L., Tempel, B.L, Papazian, D.M., Jan, Y.N. and Jan, L.Y. (1988).   Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes.  Nature 331:143-145.  [PubMed]

  39. Schwarz, T.L., Tempel, B.L, Papazian, D.M., Jan, Y.N. and Jan, L.Y. (1988).  Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila.  Nature 331:137-142.  [PubMed]

  40. Timpe, L.C. and Jan, L.Y. (1987).  Gene dosage and complementation analysis of the Shaker locus in Drosophila.  J. Neurosci. 7:1307-1317.  [PDF]

  41. Tempel, B.L., Papazian, D.M., Schwarz, T.L., Jan, Y.N. and Jan, L.Y. (1987).  Sequence of a probable K+ channel component in Drosophila deduced from Shaker cDNA.  Science 237:770-775.  [PubMed]

  42. Papazian, D.M., Schwarz, T.L., Tempel, B.L., Jan, Y.N., and Jan, L.Y. (1987).  Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila.  Science 237:749-753.  [PubMed]

  43. Jan, Y.N., Jan, L.Y. and Dennis, M.J. (1977).  Two mutations of synaptic  transmission in Drosophila.  Proc. Roy. Soc. Lond. B 198:87-108.  [PubMed]

Inwardly rectifying potassium channels

  1. Lin, Y.-F., Raab-Graham, K., Jan, Y.N., and Jan, L.Y. (2004). NO stimulation of ATP-sensitive potassium channels: Involvement of Ras/mitogen-activated protein kinase pathway and contribution to neuroprotection. Proc. Natl. Acad. Sci. USA 101:7799-7804.  [PDF]

  2. Bichet, D., Lin, Y.-F., Ibarra, C.A., Huang, C.S., Yi, B.A., Jan, Y.N., and Jan, L.Y. (2004). Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity. Proc. Natl. Acad. Sci USA 101:4441-4446.  [PDF]

  3. Bichet, D., Haass, F.A., and Jan, L.Y. (2003). Merging functional studies with structures of inward-rectifier K+ channels. Nature Reviews Neuroscience 4:957-967.  [PubMed]

  4. Hu, K., Huang, C. S., Jan, Y. N. and Jan, L. Y. (2003)  ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C.  Neuron 38:417-432.  [PubMed]

  5. Mitrovic, I., Margeta-Mitrovic, M., Bade, S., Stoffel, M., Jan, L.Y., and Basbaum, A.I. (2003)  Contribution of GIRK2-mediated postsynaptic signaling to opiate and a2-adrenergic analgesia and analgesic sex differences.  Proc. Natl. Acad. Sci USA 100:271-276.  [PDF]

  6. Ma, D., Zerangue, N. Raab-Graham, K., Fried, S.R., Jan, Y.N., and Jan, L.Y. (2002).  Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart.  Neuron 33:715-729.  [PubMed]

  7. Yi, B.A., Minor, D.L., Jr., Lin, Y.-F., Jan, Y.N., and Jan, L.Y. (2001).  Controlling potassium channel activities: interplay between the membrane and intracellular factors.  Proc. Natl. Acad. Sci. USA 98:11016-11023.  [PDF]

  8. Lu, T., Ting, A.Y., Mainland, J., Jan, L.Y., Schultz, P.G., and Yang, J. (2001). Probing ion permeation and gating in a K+ channel with backbone mutations in the selectivity filter. Nat. Neurosci. 4:239-246  [PubMed]

  9. Yi, B.A., Lin, Y.F., Jan, Y.N. and Jan, L.Y. (2001).  Yeast screen for constitutively active mutant G protein-activated potassium channels.  Neuron 29:657-667.  [PubMed]

  10. Ma, D., Zerangue, N., Lin, Y.-F., Collins, A., Yu, M., Jan, Y.N., and Jan, L.J.  (2001). Role of ER export signals in controlling surface potassium channel numbers.  Science 291:316-319.  [PubMed]

  11. Schwappach, B., Zerangue, N., Jan, Y. N. and Jan, L. Y. (2000)  Molecular basis for KATP assembly: Transmembrane interactions mediate association of a K+ channel with an ABC transporter.  Neuron 26: 155-167.  [PubMed]

  12. Lin, Y. F., Jan, Y. N. and Jan, L. Y. (2000)  Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells.  EMBO J. 19:942-955.  [PubMed]

  13. Zerangue, N., Schwappach, B., Jan, Y.N., and Jan, L.Y. (1999).  A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane KATP channels.  Neuron 22:537-548.  [PubMed]

  14. Minor, D.L. Jr., Masseling, S.J., Jan, Y.N., and Jan, L.Y. (1999).  Transmembrane structure of an inwardly rectifying potassium channel.  Cell 96:879-891.  [PubMed]

  15. Chuang, H.-h., Yu, M., Jan, Y.N. and Jan, L.Y. (1998).  Evidence that the nucleotide exchange and hydrolysis cycle of G-proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.  Proc. Natl. Acad. Sci. USA 95:11727-11732.  [PDF]

  16. Ford, C.E., Skiba, N.P., Bae, H., Daaka, Y., Reuveny, E., Shekter, L.R., Rosal, R., Weng, G., Yang, C.-S., Iyengar, R., Miller, R.J., Jan, L.Y., Lefkowitz, R.J., Hamm, H.E. (1998).  Molecular basis for interactions of G protein βγ subunits with effectors.  Science 280:1271-1274.  [PubMed]

  17. Lüscher, C., Jan, L.Y., Stoffel, M., Malenka, R.C. and Nicoll, R.A. (1997).  G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter action in hippocampal neurons.  Neuron 19:687-695.  [PubMed]

  18. Slesinger, P.A., Stoffel, M., Jan, Y.N. and Jan, L.Y. (1997).  Defective γ-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice.  Proc. Natl. Acad. Sci. USA 94:12210-12217.  [PDF]

  19. Chuang, H.H., Jan, Y.N. and Jan, L.Y. (1997).  Regulation of IRK3 inward rectifier K+ channel by m1 acetylcholine receptor and intracellular magnesium.  Cell 89:1121-1132.  [PubMed]

  20. Collins, A. Chuang, H.H., Jan, Y.N. and Jan, L.Y. (1997),  Scanning mutagenesis of the putative transmembrane segments of Kir 2.1, an inward rectifier potassium channel.  Proc. Natl. Acad. Sci. USA 94:5456-5460.  [PDF]

  21. Huang, C.L., Jan, Y.N. and Jan, L.Y. (1997)  Binding of the G protein βγ subunit to multiple regions of G protein-gated inward rectifying K+ channels.  FEBS Lett. 405:291-298.  [PubMed]

  22. Yang, J., Yu, M., Jan, Y.N. and Jan, L.Y. (1997).  Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel.  Proc. Natl. Acad. Sci. USA 94:1568-1572.  [PDF]

  23. Signorini, S., Liao, Y.J., Duncan, S.A., Jan, L.Y. and Stoffel, M. (1997).  Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.  Proc. Natl. Acad. Sci. USA 94:923-927.  [PDF]

  24. Vivaudou, M., Chan, K.W., Sui, J.L., Jan, L.Y., Reuveny, E. and D.E. Logothetis (1997).  Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.  J. Biol. Chem. 272:31553-31560.  [PDF]

  25. Jan, L.Y. and Jan, Y.N. (1997).  Voltage-gated and inwardly rectifying potassium channels. J. Physiol. 505:267-282.  [PDF]

  26. Fakler, B., Schultz, J.H., Yang, J., Schulte, U., Brändle, U., Zenner, H.P., Jan, L.Y. and Ruppersberg, J.P. (1996).  Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.  EMBO J. 15:4093-4099.  [PubMed]

  27. Liao, Y.J., Jan, Y.N. and Jan, L.Y. (1996).  Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brains.  J. Neurosci. 16:7137-7150.  [PDF]

  28. Tinker, A., Jan, Y.N. and Jan, L.Y. (1996).  Regions responsible for the assembly of inwardly rectifying potassium channels.  Cell 87:857-868.  [PubMed]

  29. Slesinger, P.A., Patil, N. Liao Y.J., Jan, Y.N., Jan, L.Y. and Cox, D.R. (1996).  Functional effects of the mouse weaver mutation on G protein-gated inwardly rectifying K+ channels.  Neuron 16: 321-331.  [PubMed]

  30. Reuveny, E. Jan, Y.N. and Jan, L.Y. (1996).  Contributions of a negatively charged residue in the hydrophobic domain of the IRK1 inwardly rectifying K+ channel to K+-selective permeation.  Biophys. J. 70: 754-761  [PubMed]

  31. Collins, A., German, M.S., Jan, Y.N., Jan, L.Y. and Zhao, B. (1996).  A strongly inwardly rectifying K+ channel that is sensitive to ATP.  J.Neurosci. 16:1-9.  [PubMed]

  32. Yang, J., Jan, Y.N. and Jan, L.Y. (1995).  Determination of the subunit stoichiometry of an inwardly rectifying potassium channel.  Neuron 15:1441-1447.  [PubMed]

  33. Slesinger, P.A., Reuveny, E., Jan, Y.N. and Jan, L.Y. (1995).  Identification of structural elements involved in G protein gating of the GIRK1 potassium channel.  Neuron 15:1145-1156.  [PubMed]

  34. Huang, C-L., Slesinger, P.A., Casey, P.J., Jan, Y.N. and Jan, L.Y. (1995).  Evidence that direct binding of Gßγ to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.  Neuron 15:1133-1143.  [PubMed]

  35. Yang, J., Jan, Y.N. and Jan, L.Y. (1995).  Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel.  Neuron 14:1047-1054.  [PubMed]

  36. Reuveny, E., Slesinger, P.A., Inglese, J., Morales, J.M., Iñiguez-Lluhi, J.A., Lefkowitz, R.J., Bourne, H.R., Jan, Y.N. and Jan, L.Y. (1994).  Activation of the cloned muscarinic potassium channel by G protein βγ subunits.  Nature 370:143-146.  [PubMed]

  37. Kubo, Y., Reuveny, E., Slesinger, P.A., Jan, Y.N. and Jan, L.Y. (1993).  Primary structure and functional expression of a rat G protein coupled muscarinic potassium channel.  Nature 364:802-806.  [PubMed]

  38. Kubo, Y., Baldwin, T.J., Jan, Y.N. and Jan, L.Y. (1993).  Primary structure and functional expression of a mouse inward rectifier potassium channel.  Nature 362:127-133.  [PubMed]

Trafficking channels and receptors

  1. Ma, D., and Jan, L.Y. (2002). ER transport signals and trafficking of potassium channels and receptors. Curr. Opin. Neurobiol. 12:287-292.  [PubMed]

  2. Gu, C., Jan, Y. N., and Jan, L. Y. (2003)  A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channel. Science 301:646-649.  [PubMed]

  3. Hu, K., Huang, C. S., Jan, Y. N. and Jan, L. Y. (2003)  ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C.  Neuron 38:417-432.  [PubMed]

  4. Ma, D., and Jan, L.Y. (2002).  ER transport signals and trafficking of potassium channels and receptors.  Curr. Opin. Neurobiol. 12:287-292.  [PubMed]

  5. Ma, D., Zerangue, N. Raab-Graham, K., Fried, S.R., Jan, Y.N., and Jan, L.Y. (2002).  Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart.  Neuron 33:715-729.  [PubMed]

  6. Zerangue, N., Malan, M.J., Fried, S.R., Dazin, P.F., Jan, Y.N., Jan, L.Y., and Schwappach, B. (2001).  Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells.  Proc. Natl. Acad. Sci. USA 98: 2431-2436.  [PDF]

  7. Ma, D., Zerangue, N., Lin, Y.-F., Collins, A., Yu, M., Jan, Y.N., and Jan, L.J. (2001).  Role of ER export signals in controlling surface potassium channel numbers.  Science 291:316-319.  [PubMed]

  8. Margeta-Mitrovic, M., Jan, Y.N., and Jan, L.Y. (2000).  A trafficking checkpoint controls GABAB receptor heterodimerization.  Neuron 27:97-106.  [PubMed]

  9. Whistler, J.L., Chuang, H.-H., Chu, P., Jan, L.Y., and von Zastrow, M. (1999).  Functional Dissociation of m opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction.  Neuron 23:737-746.  [PubMed]

  10. Zerangue, N., Schwappach, B., Jan, Y.N., and Jan, L.Y. (1999).  A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane KATP channels.  Neuron 22:537-548.  [PubMed]

Channel families-evolution

  1. Bichet, D., Lin, Y.-F., Ibarra, C.A., Huang, C.S., Yi, B.A., Jan, Y.N., and Jan, L.Y. (2004). Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity. Proc. Natl. Acad. Sci USA 101:4441-4446.  [PDF]

  2. Jan, L.Y. and Jan, Y.N. (1997).  Cloned potassium channels from eukaryotes and prokaryotes.  Annu. Rev. Neurosci. 20:91-123.  [PubMed]

  3. Jan, L.Y. and Jan, Y.N. (1994).  Potassium channels and their evolving gates.  Nature 371:119-122.  [PubMed]

  4. Jan, L.Y. and Jan, Y.N. (1992).  Tracing the roots of ion channels.  Cell 69:715-718.  [PubMed]

  5. Jan, L.Y. and Jan, Y.N. (1990).  How might the diversity of potassium channels be generated?  Trends Neurosci. 13:413-419.  [PubMed]

  6. Jan, L.Y. and Jan, Y.N. (1990).  A superfamily of ion channels.  Nature 345:672.  [PubMed]

New fluorescent probes for studying channel function

  1. Cohen, B.E., Pralle, A., Yao, X-J, Swaminath, G., Gandhi, C., Jan, Y.N., Kobilka, B.K., Isacoff, E.Y., and Jan, L.Y. (2005).  A fluorescent probe designed for studying protein conformational change.  Proc. Natl. Acad. Sci. USA 102:965-970.  [PubMed]

  2. Cohen, B.E., McAnaney, T.B., Park, E.S., Jan, Y.N., Boxer, S.G., and Jan, L.Y. (2002)   Probing protein electrostatics with a synthetic fluorescent amino acid.  Science 296:1700-1703.   [Abstract]  [PubMed]

Potassium channels and disease

  1. Cooper, E.C., and Jan, L.Y. (2003).  M-channels: neurological diseases, neuromodulation, and drug development.  Arch. Neurol. 60:496-500.  [PubMed]

  2. Mitrovic, I., Margeta-Mitrovic, M., Bade, S., Stoffel, M., Jan, L.Y., and Basbaum, A.I. (2003)  Contribution of GIRK2-mediated postsynaptic signaling to opiate and a2-adrenergic analgesia and analgesic sex differences.  Proc. Natl. Acad. Sci USA 100:271-276.   [PDF]

  3. Pei, L., Wiser, O., Slavin, A., Mu, D., Powers, S., Jan, L. Y. and Hoey, T. (2003)  Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.  Proc. Natl. Acad. Sci. U.S.A. Early Edition [PDF]

  4. Mu, D., Chen, L., Zhang, X., See, L.-H., Koch, C.M., Yen, C., Tong, J.J., Spiegel, L., Nguyen, K.C.Q., Servoss, A., Peng, Y., Pei, L., Marks, J.R., Lowe, S., Hoey, T., Jan, L.Y., McCombie, W.R., Wigler, M.H., and Powers, S. (2003).  Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene.  Cancer Cell 3:297-302.  [PubMed]

  5. Cooper, E. C., Aldape, K. D., Abosch, A., Barbaro, N. M. Berger, M. S. Peacock, W. S. Jan, Y. N. and Jan, L. Y. (2000)  Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.  Proc. Natl. Acad. Sci. USA 97: 4914-4919.   [PubMed]

  6. Cooper, E.C. and Jan, L.Y. (1999).  Ion channel genes and human neurological disease: recent progress, prospects, and challenges.  Proc. Natl. Acad. Sci. USA 96:4759-4766.   [PDF]

  7. Stoffel, M. and Jan, L.Y. (1998).  Epilepsy genes: excitement traced to K+ channels.  Nature Genetics 18:6-8.  [PubMed]

Drosophila Nervous System

  1. Abdelilah-Seyfried, S., Chan, Y.-M., Zeng, C., Justice, N.J., Younger-Shepherd, S., Sharp, L.E., Barbel, S., Meadows, S.A., Jan, L.Y., and Jan, Y.N. (2000). A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ. Genetics 155:733-752.  [PDF]

  2. Lane, M.E., Sauer, K., Wallace, K., Jan, Y.N., Lehner, C.F., and Vaessin, H. (1996). Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell 87:1225-1235.  [PubMed]

  3. Feger, G., Vaessin, H., Su, T.T., Wolff, E., Jan, L.Y. and Jan, Y.N. (1995). dpa, a member of the MCM family, is required for mitotic DNA replication but not endoreplication in Drosophila. EMBO J. 14:5387-5398.  [PubMed]

  4. Giniger, E., Jan, L.Y. and Jan, Y.N. (1993). Specifying the path of the intersegmental nerve of the Drosophila embryo: a role for Delta and Notch. Development 117:431-440.  [PDF]

  5. Jan, Y.N. and Jan, L.Y. (1993). Peripheral Nervous System. In The Development of Drosophila melanogaster, ed. M. Bate and A. Martinez-Arias, Chapter 20, pp. 1207-1244. Cold Spring Harbor Press, Cold Spring Harbor, New York.  

  6. Bellen, H., Vaessin, H., Bier, E., Kolodkin, A., D'Evelyn, D., Kooyer, S., and Jan, Y.N. (1992). The Drosophila couch potato gene: an essential gene required for normal adult behavior. Genetics 131:365-375.  [PDF]

  7. Hartenstein, V. and Jan, Y.N. (1992). Studying Drosophila Embryogenesis with P-lacZ Enhancer Trap Lines. Roux's Arch. Dev. Biol. 201:194-220.  

  8. Bier, E., Vaessin, H., Shepherd, S., Lee, K., McCall, K., Barbel, S., Ackerman, L., Carretto, R., Uemura, T., Grell, E., Jan, L.Y. and Jan, Y.N. (1989). Searching for Pattern and Mutation in the Drosophila Genome with a P-lacZ Vector. Genes Dev. 3:1273-1287.  

  9. Katz, F., Moats, W., and Jan, Y.N. (1988). A carbohydrate epitope expressed uniquely on the cell surface of Drosophila neurons is altered in the mutant nac (neurally altered carbohydrate). EMBO J. 7:3471-3477  [PubMed]

  10. Bier, E., Ackerman, L., Barbel, S., Jan, L.Y. and Jan, Y.N. (1988). Identification and characterization of a neuron-specific nuclear antigen in Drosophila. Science 240: 913-916.  [PubMed]

  11. Jan, Y.N., Bodmer, R., Jan, L.Y., Ghysen, A., and Dambly-Chaudière, C. (1987). Mutations affecting the embryonic development of the peripheral nervous system in Drosophila. In Molecular Entomology, ed. Liss, Alan R., 49:45-56. New York.  

  12. Ghysen, A., Dambly-Chaudiere, C., Aceves, E., Jan, L.Y. and Jan, Y.N. (1986). Sensory neurons and peripheral pathways in Drosophila embryos. Roux's Arch. Dev. Biol. 195:281-289.  

  13. Ghysen, A., Jan, L.Y. and Jan, Y.N. (1985). Segmental determination in Drosophila central nervous system. Cell 40:943-948.  [PubMed]

  14. Jan, Y.N., Ghysen, A., Christoph, I., Barbel, S. and Jan, L.Y. (1985). Formation of neuronal pathways in the imaginal discs of Drosophila melanogaster. J. Neurosci. 5:2453-2464.  [PubMed]

  15. Ghysen, A., Dambly-Chaudiere, C., Jan, L.Y. and Jan, Y.N. (1982). Segmental differences in the protein content of Drosophila imaginal discs. EMBO J. 1:1373-1379.  

  16. Jan, L.Y. and Jan, Y.N. (1982) Antibodies to horseradish peroxidase as a neuronal marker in Drosophila and in grasshopper embryos. Proc. Natl. Acad. Sci. USA 79:2700-2704.  [PubMed]

Dendrite Development and Neuronal Morphogenesis

  1. Grueber, W.B., Yang, C.H., Ye, B., and Jan, Y.N. (2005). The development of neuronal morphology in insects. Curr Biol. 15:R730-R738.  [PubMed]

  2. He, Y., Emoto, K., Fang, X., Ren, N., Tian, X., Jan, Y.N., and Adler, P.N. (2005). Drosophila Mob Family Proteins Interact with the Related Tricornered (Trc) and Warts (Wts) Kinases. Mol. Biol. Cell. 16:4139-4152.  [PubMed]

  3. Goldstein, A.Y.N., Jan, Y.N., and Luo, L. (2005). Function and regulation of Tumbleweed (RacGAP50C) in neuroblast proliferation and neuronal morphogenesis. Proc. Natl. Acad. Sci. USA 102:3834-3839.  [PubMed]

  4. He, Y., Fang, X., Emoto, K., Jan, Y.N., and Adler, P.N. (2005). The tricornered Ser/Thr protein kinase is regulated by phosphorylation and interacts with furry during Drosophila wing hair development. Mol. Biol. Cell 16:689-700.  [PubMed]

  5. Ye, B., and Jan, Y.N. (2005). The cadherin superfamily and dendrite development. TRENDS Cell Biol. 15:64-67.  [PubMed]

  6. Huang, E.J., Li, H.h., Tang, A.A., Wiggins, A.K., Neve, R.L., Zhong, W., Jan, L.Y. and Jan, Y.N. (2005). Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization. Genes Dev. 19:138-151.  [PubMed]

  7. Shi, S.-H., Cheng, T., Jan, L.Y., and Jan, Y.N. (2004). APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr. Biol. 14:2025-2032.  [PubMed]

  8. Shi, S.-H., Cox, D.N., Wang, D., Jan, L.Y., and Jan, Y.N. (2004). Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1). Proc. Natl. Acad. Sci. USA 101:13341-13345.  [PDF]

  9. Shi, S.-H., Cheng, T., Jan, L.Y., and Jan, Y.N. (2004). The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation. Proc. Natl. Acad. Sci. USA 101:13346-13351.  [PDF]

  10. Emoto, K., He, Y., Ye, B., Grueber, W.B., Adler, P.N., Jan, L.Y., and Jan, Y.N. (2004). Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons. Cell 119:245-256.  [PubMed]

  11. Ye, B., Petritsch, C., Clark, I.E., Gavis, E.R., Jan, L.Y., and Jan, Y.N. (2004). nanos and pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Current Biology, 14:314-321.  [PubMed]

  12. Grueber, W.B., and Jan, Y.N. (2004). Dendritic development: lessons from Drosophila and related branches. Curr. Opin. Neurobiol. 14:74-82.  [PubMed]

  13. Jan, Y.N., and Jan, L.Y. (2003). The control of dendrite development. Neuron 40:229-242.  [PubMed]

  14. Rothenberg, M.E., Rogers, S.L., Vale, R.D., Jan, L.Y., and Jan, Y.N. (2003).  Drosophila Pod-1 crosslinks both actin and microtubules and controls the targeting of axons. Neuron 39:779-791.  [PubMed]

  15. Grueber, W.B.*, Ye, B.*, Moore, A.W., Jan L.Y., and Jan, Y.N. (2003). Dendrites of distinct classes of Drosophila sensory neurons show different capacities for homotypic repulsion. Curr. Biol. 13:618-626. (* = equal contribution).  [PubMed]

  16. Grueber, W.B., Jan, L.Y., and Jan, Y.N. (2003). Different levels of the homeodomain protein Cut regulate distinct dendrite branching patterns of Drosophila multidendritic neurons. Cell 112:805-818.  [PubMed]

  17. Shi, S.-H., Jan, L.Y., and Jan, Y.-N. (2003)  Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity.  Cell 112:63-75.  [PubMed]

  18. Moore, A.W., Jan, L.Y., and Jan, Y.N. (2002). hamlet, a binary genetic switch between single and multiple dendrite neuron morphology. Science 297: 1355-1358.  [PubMed]

  19. Grueber, W.B., Jan, L.Y., and Jan, Y.N. (2002). Tiling of the Drosophila epidermis by multidendritic sensory neurons. Development 129:2867-2878.  [PDF]

  20. Brenman, J.E., Gao, F-B., Jan, L.Y., and Jan, Y.N. (2001). Sequoia, a tramtrack-related zinc finger protein, functions as a pan-neural regulator for dendrite and axon morphogenesis in Drosophila. Dev. Cell 1:667-677.  [PubMed]

  21. Jan, Y.N. and Jan, L.Y. (2001). Dendrites. Genes Dev. 15:2627-2641.  [PDF]

  22. Gao, F.-B., Kohwi, M., Brenman, J.E., Jan, L.Y., and Jan, Y.N. (2000). Control of dendritic field formation in Drosophila: The roles of flamingo and competition between homologous neurons. Neuron 28:91-101.  [PubMed]

  23. Hassan, B.A., Bermingham, N.A., He, Y., Sun, Y., Jan, Y.N., Zoghbi, H.Y. and Bellen, H.J. (2000) Atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain. Neuron 25: 549-561.  [PubMed]

  24. Gao, G.-B., Brenman, J.E., Jan, L.Y., Jan, Y.N. (1999). Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 13:2549-2561.  [PDF]

  25. Luo, L., Jan, L.Y. and Jan, Y.N. (1997). Rho family small GTP-binding proteins in growth cone signalling. Curr. Opin. Neurobiol. 7:81-86.  [PubMed]

  26. Luo, L., Lee, T., Tsai, L., Tang, G., Jan, L.Y. and Jan, Y.N. (1997). Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization. Proc. Natl. Acad. Sci. USA 94:12963-12968.  [PDF]

  27. Kolodziej, P.A. Timpe, L.C., Mitchell, K.J., Fried, S.R., Goodman, C.S., Jan, L.Y. and Jan, Y.N. (1996). frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell 87:197-204.  [PubMed]

  28. Luo, L., Hensch, T.K., Ackerman, L., Barbel, S., Jan, L.Y and Jan, Y.N. (1996). Differential effects of the Rac GTPase on purkinje cell axons, dendrites and dendritic spines. Nature 379:837-840.  [PubMed]

  29. Eaton, S., Auvien, P., Luo, L., Jan, Y.N. and Simons, K. (1995). CDC42 and Rac1 control different actin dependent processes in the Drosophila wing disc epithelium. J. Cell. Biol. 131:151-164.  [PDF]

  30. Kolodziej, P., Jan, L.Y., and Jan, Y.N. (1995). Mutations that affect the length, fasciculation and ventral orientation of specific axons in the Drosophila embryo. Neuron 15:273-286.  [PubMed]

  31. Luo, L., Liao, Y.J., Jan, L.Y. and Jan, Y.N. (1994) Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev. 8:1787-1802.  [PubMed]

  32. Giniger, E., Wells, W.A.E., Jan, L.Y. and Jan, Y.N. (1993). Tracing neurons with a Kinesin-ß-Galactosidase fusion protein. Roux's Arch. Dev. Biol. 202:112-122.  

  33. Bodmer, R. and Jan, Y.N. (1987). Morphological differentiation of the embryonic peripheral neurons in Drosophila. Roux's Arch. Dev. Biol. 196:69-77.  

Cell fate specification, mostly neuronal

  1. Moore, A.W., Roegiers, F., Jan, L.Y., and Jan, Y.N. (2004). Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification. Genes Dev 18:623-628.  [PubMed]

  2. Rothenberg, M., and Jan, Y.N. (2003). The hippo hypothesis. Nature 425:469- 470.  [PubMed]

  3. Rothenberg, M., and Jan, Y. (2002). salvador-The persistence of proliferation. Cancer Cell 2:171-173.   [PubMed]

  4. Justice, N.J., and Jan, Y.N. (2002).  Variations on the Notch pathway in neural development  Curr. Opin. Neurobiol., 12: 64-70  [PubMed]

  5. Sun, Y., Jan, L.Y., and Jan, Y.N. (2000).  Ectopic scute induces Drosophila ommatidia development without R8 founder photoreceptors.  Proc. Natl. Acad. Sci. 97:6815-6819.  [PDF]

  6. Chan, Y.M. and Jan, Y.N. (1999).  Conservation of neurogenic genes and mechanisms.  Curr. Opin. Neurobiol.5:582-588.  [PubMed]

  7. Chan, Y.M. and Jan, Y.N. (1999).  Presenilins, processing of Β-amyloid precursor protein, and notch signaling.  Neuron 23:201-204.  [PubMed]

  8. Chan, Y.M. and Jan, Y.N. (1998).  Roles for proteolysis and trafficking in Notch maturation and signal transduction.  Cell 94:423-426.  [PubMed]

  9. Sun, Y., Jan, L.Y. and Jan, Y.N. (1998).  Transcriptional regulation of atonal during development of the Drosophila peripheral nervous system.  Development 125:3731-3740.  [PDF]

  10. Zeng, C., Justice, N.J., Abdelilah, S., Chan, Y.-M., Jan, L.Y. and Jan, Y.N. (1998).  The Drosophila LIM-only gene, dLMO, is mutated in Beadex alleles and might represent an evolutionarily conserved function in appendage development.  Proc. Natl. Acad. Sci. USA 95:10637-10642.  [PDF]

  11. Doherty, D., Jan, L.Y. and Jan, Y.N. (1997).  The Drosophila neurogenic gene big brain, which encodes a membrane-associated protein, acts cell autonomously and can act synergistically with Notch and Delta.  Development, 124:3881-3893.  [PDF]

  12. Lage, P.Z., Jan, Y.N., and Jarman, A.P. (1997).  Requirement for EGF receptor signalling in neural recruitment during formation of Drosophila chordotonal sense organ clusters.  Curr. Biol. 7:166-175.  [PubMed]

  13. Anderson, D.J. and Jan, Y.N. (1997).  The Determination of the Neuronal Phenotype.  In Molecular and Cellular Approaches to Neural Development, ed. W.M. Cowan, T.M. Jessell and S.L. Zipursky, pp. 26-63. Oxford University Press, Oxford, United Kingdom.  

  14. Chien, C.T., Hsiao, C.D., Jan, L.Y. and Jan, Y.N. (1996).  Neuronal type information encoded in the basic-helix-loop-helix domain of proneural genes.  Proc. Natl. Acad. Sci. USA 93:13239-13244.  [PDF]

  15. Doherty, D., Feger, G., Younger-Shephard, S., Jan, L.Y. and Jan, Y.N. (1996).  Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, In Drosophila wing formation.  Genes Dev. 10:421-434.  [PubMed]

  16. Jarman, A.P., Sun, Y., Jan, L.Y. and Jan, Y.N. (1995).  Role of the proneural gene, atonal in formation of Drosophila chordotonal organs and photoreceptors.  Development 121:2019-2030.  [PDF]

  17. Vaessin, H., Brand, M., Jan, L.Y. and Jan, Y.N. (1994).  daughterless is essential for neuronal precursor differentiation but not for initiation of neuronal precursor formation in Drosophila embryo.  Development 120:935-945.  [PDF]

  18. Jarman, A.P., Grell, E.H., Ackerman, L., Jan, L.Y. and Jan, Y.N. (1994).  atonal is the proneural gene for Drosophila photoreceptors.  Nature 369:398-400.  [PubMed]

  19. Jan, Y.N. and Jan, L.Y. (1994).  Genetic control of cell fate specification in Drosophila peripheral nervous system.  Annu. Rev. of Genet. 28:373-393.  [PubMed]

  20. Jan, Y.N. and Jan, L.Y. (1994).  Neuronal cell fate specification in Drosophila.  Curr. Opin. Neurobiol. 4:8-13.  [PubMed]

  21. Jan, Y.N. and Jan, L.Y. (1993).  HLH protein, fly neurogenesis and vertebrate myogenesis.  Cell 75:827-830.  [PubMed]

  22. Ghysen, A., Dambly-Chaudière, C., Jan, L.Y. and Jan, Y.N. (1993).  Cell interaction and gene interaction in peripheral neurogenesis.  Genes Dev. 7:723-733.  [PubMed]

  23. Jarman, A.P., Grau, Y., Jan, L.Y. and Jan, Y.N. (1993).  atonal is a proneural gene for chordotonal organs in the Drosophila peripheral nervous system.  Cell 73:1307-1321.  [PubMed]

  24. Jarman, A.P., Brand, M., Jan, L.Y. and Jan, Y.N. (1993).  The regulation and function of helix-loop-helix gene, asense, in Drosophila neural precursors.  Development 119:19-29.  [PDF]

  25. Brand, M., Jarman, A.P., Jan, L.Y. and Jan, Y.N. (1993).  asense is a Drosophila neural precursor gene and is capable of initiating sense organ formation.  Development 119:1-17.  [PDF]

  26. Bodmer, R., Jan, L.Y. and Jan, Y.N. (1993).  A late role for a subset of neurogenic genes to limit sensory precursor recruitments in Drosophila embryos.  Roux's Arch. Dev. Biol. 202:371-381.  

  27. Blochlinger, K., Jan, L.Y. and Jan, Y.N. (1993).  Post-embryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila.  Development 117:441-450.  [PDF]

  28. Bier, E., Vaessin, H., Younger-Shepherd, S., Jan, L.Y. and Jan, Y.N. (1992).  deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product.  Genes Dev. 6:2137-2151.  [PubMed]

  29. Rao, Y., Bodmer, R., Jan, L.Y. and Jan Y.N. (1992).  The big brain gene of Drosophila functions to control the number of neuronal precursors in the peripheral nervous system.  Development 116:31-40.  [PDF]

  30. Younger-Shepherd, S., Vaessin, H., Bier, E., Jan, L.Y., and Jan, Y.N. (1992).  deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination.  Cell 70:911-922.  [PubMed]

  31. Rutledge, B. J., Zhang, K., Bier, E., Jan, Y.N. and Perrimon, N. (1992).  The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.  Genes Dev. 6:1503-1517.  [PubMed]

  32. Jan, Y. N. and Jan, L.Y. (1992).  Neuronal specification.  Curr. Opin. Genet. Dev. 2:608-613.  [PubMed]

  33. Boulianne, G.L, de la Concha, A., Campos-Ortega, J.A., Jan, L.Y. and Jan, Y.N. (1991).  The Drosophila neurogenic gene neuralized encodes a protein with a novel putative DNA-binding motif.  EMBO J. 10:2975-2983.  [PubMed]

  34. Rao, Y., Jan, L.Y. and Jan, Y.N. (1991).  Neuroectoderm in Drosophila embryos is dependent on the mesoderm for positioning but not for formation.  Genes Dev. 5:1577-1588.  [PubMed]

  35. Blochlinger, K., Jan, L.Y. and Jan, Y.N. (1991).  Transformation of sensory organ identity by ectopic expression of Cut in Drosophila.  Genes Dev. 5:1124-1135.  [PubMed]

  36. Campos-Ortega, J. and Jan, Y.N. (1991).  Genetic and molecular bases of neurogenesis in Drosophila melanogaster.  Annu. Rev. Neurosci. 14:399-420  [PubMed]

  37. Jan, Y.N. and Jan, L.Y. (1990).  Genes required for specifying cell fates in Drosophila embryonic sensory nervous system.  Trends Neurosci. 13:493-498.  [PubMed]

  38. Vaessin, H., Caudy, M., Bier, E., Jan, L.Y. and Jan, Y.N. (1990).  The role of helix-loop-helix proteins in Drosophila neurogenesis.  Cold Spring Harbor Symposia on Quantitative Biology LV: 239-245.  [PubMed]

  39. Bodmer, R., Jan, L.Y. and Jan, Y.N. (1990).  A new homeobox-containing gene, msh-2, is transiently expressed early during mesodcerm formation of Drosophila.  Development 110:661-670.  [PubMed]

  40. Blochlinger, K., Bodmer, R., Jan, L.Y. and Jan, Y.N. (1990).  Patterns of expression of Cut, a protein required for external sensory organ development in wild-type and cut mutant Drosophila embryos.  Genes Dev. 4:1322-1331.  [PubMed]

  41. Rao,Y., Jan, L.Y. and Jan, Y.N. (1990).  Similarity of the product of the Drosophila neurogenic gene big brain to transmembrane channel proteins.  Nature 345:163-167.  [PubMed]

  42. Bier, E., Jan, L.Y. and Jan, Y.N. (1990).  rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster.  Genes Dev. 4:190-203.  [PubMed]

  43. Jan, Y.N. and Jan, L.Y. (1989).  Genes involved in early neural development of Drosophila.  In The Assembly of the Nervous System. 47th Symposium of Soc. of Dev. Biology, pp. 1-16. Alan R. Liss, Inc., New York.  

  44. Murre, C., Schonleber McCaw, P., Vaessin, H., Caudy, M., Jan, L.Y., Jan, Y.N., Cabrera, C.V., Buskin, J.N., Hauschka, S.D., Lassar, A.B., Weintraub, H. and Baltimore, D. (1989).  Heterodimers of helix-loop-helix proteins bind specifically to a common DNA sequence.  Cell 58:537-544.  [PubMed]

  45. Caudy, M., Vaessin, H., Brand, M., Tuma, R., Jan, L.Y. and Jan, Y.N. (1988).  daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex.  Cell 55:1061-1067.  [PubMed]

  46. Dambly-Chaudiere, C., Ghysen, A., Jan, L.Y. and Jan, Y.N. (1988).  The determination of sense organs in Drosophila: interaction of scute with daughterless.  Roux's Arch. Dev. Biol. 197:419-423.  

  47. Caudy, M., Grell, E., Dambly-Chaudiere, C., Ghysen, A., Jan, L.Y. and Jan, Y.N. (1988).  The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila.  Genes Dev. 2:843-852.  [PubMed]

  48. Blochlinger, K.B., Bodmer, R., Jack, J., Jan, L.Y. and Jan, Y.N. (1988).  Primary structure and expression of a product from cut, a locus involved in specifying sensory organ identity in Drosophila.  Nature 333:629-635.  [PubMed]

  49. Bodmer, R., Jan Barbel, S., Shepherd, S., Jack, J.W., Jan, L.Y. and Jan, Y.N. (1987).  Transformation of sensory organs by mutations of the cut locus of Drosophila melanogaster.  Cell 51: 293-307.  [PubMed]

Asymmetric division

  1. Kuo, C.T., and Jan, Y.N. (2005). The hand that rocks the spindle. Nat. Cell Biol. 7:858-859.  [PubMed]

  2. Roegiers, F., Jan, L.Y., and Jan, Y.N. (2005). Regulation of membrane localization of sanpodo by lethal giant larvae and neuralized in asymmetrically dividing cells of Drosophila sensory organs. Mol. Biol. Cell. 16:3480-3487.  [PubMed]

  3. Lai, E.C., Roegiers, F., Qin, X., Jan, Y.N., and Rubin, G.M. (2005). The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta. Development 132:2319-2332.  [PubMed]

  4. Roegiers, F., and Jan, Y.N. (2004). Asymmetric cell division. Curr. Opin. Cell Biol. 16:195-205.  [PubMed]

  5. Li, H.-S., Wang, D., Shen, Q., Schonemann, M.D., Gorski, J.A., Jones, K.R., Temple, S., Jan, L.Y., and Jan, Y.N. (2003). Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron 40:1105-1118.  [PubMed]

  6. Justice, N.J., Roegiers, F.R., Jan, L.Y., and Jan, Y.N. (2003). Lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage. Curr. Biol. 13:778-783.  [PubMed]

  7. Justice, N.J., and Jan, Y.N. (2003). A lethal giant kinase in cell polarity. Nat. Cell Biol. 5:273-274.  [PubMed]

  8. Petritsch, C., Tavosanis, G., Turck, C.W., Jan, L.Y., and Jan, Y.N. (2003)  The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts.  Dev. Cell 4, 273-281.  [PubMed]

  9. Petersen, P.H., Zou, K., Hwang, J.K., Jan, Y.N., and Zhong, W. (2002)  Progenitor cell maintenance requires numb and numblike during mouse neurogenesis.  Nature 419:929-934.  [PubMed]

  10. Shen, Q., Zhong, W., Jan, Y.N., and Temple, S. (2002).  Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts.  Development 129:4843-4853.  [PDF]

  11. Jan, Y.N. and Jan, L.Y. (2001).  Asymmetric cell division in the Drosophila nervous system.  Nature Revs. Neurosci. 2:772-779.  [PubMed]

  12. Hong, Y., Stronach, B., Perrimon, N., Jan, L.Y. and Jan, Y.N. (2001).  Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts.  Nature 414:634-638.  [PubMed]

  13. Roegiers, F., Younger-Shepherd, S., Jan, L.Y. and Jan, Y.N. (2001).  Bazooka is required for localization of determinants and controlling proliferation in the sensory organ precursor cell lineage in Drosophila.  Proc. Natl. Acad. Sci USA 98:14469-14474.  [PDF]

  14. Sun, T.-Q., Lu, B., Feng, J.-J., Reinhard, C., Jan, Y.N., Frantl, W.J., and Williams, L.T. (2001).  PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signaling.  Nature Cell Biol. 3:628-636.  [PubMed]

  15. Lu, B., Roegiers, F., Jan, L.Y., and Jan, Y.N. (2001).  Adherens junctions inhibit asymmetric division in the Drosophila epithelium.  Nature 409:522-525.  [PubMed]

  16. Roegiers, F., Younger-Shepherd, S., Jan, L.Y., and Jan, Y.N. (2001).  Two types of asymmetric divisions in the Drosophila sensory organ precursor cell lineage.  Nature Cell Biol. 3:58-67.  [PubMed]

  17. Lu, B., Jan, L.Y. and Jan, Y.N. (2000).  Control of Cell Divisions in the Nervous System: Symmetry and Asymmetry.  Annu. Rev. Neurosci. 23:531-556.  [PubMed]

  18. Jan, Y.N. and Jan, L.Y. (2000).  Polarity in cell division: What frames they fearful asymmetry?  Cell:599-602.  [PubMed]

  19. Jan, Y.N. and Jan, L.Y. (1999).  Asymmetry across species.  Nature Cell Biol. 1:E42-E44.  [PubMed]

  20. Lu, B., Ackerman, L., Jan, L.Y., and Jan, Y.N. (1999).  Modes of protein movement that lead to the asymmetric localization of Partner of numb during Drosophila neuroblast division.  Molecul. Cell 4:883-891.  [PubMed]

  21. Lu, B., Usui, T., Uemura, T., Jan, L., and Jan, Y.N. (1999).  Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila.  Curr. Biol. 9:1247-1250.  [PubMed]

  22. Knoblich, J.A., Jan, L.Y., and Jan, Y.N. (1999).  Deletion analysis of the Drosophila Inscuteable protein reveals domains for cortical localization and asymmetric localization.  Curr. Biol. 9:155-158.  [PubMed]

  23. Lu, B., Rothenberg, M., Jan, L.Y. and Jan, Y.N. (1998).  Partner of Numb, a novel protein that colocalizes with Numb during mitosis, directs Numb asymmetric localization in Drosophila neural and muscle progenitors.  Cell 95:225-235.  [PubMed]

  24. Shen, C.-P., Knoblich, J.A., Chan, Y.-M., Jiang, M.-M., Jan, L.Y. and Jan, Y.N. (1998).  Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila.  Genes Dev. 12:1837-1846.  [PDF]

  25. Zeng C., Younger-Shepherd S., Jan L.Y., Jan Y.N. (1998).  Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage.  Genes Dev. 12:1086-1091.  [PDF]

  26. Chien, C.-T., Wang, S., Rothenberg, M., Jan, L.Y. and Jan, Y.N. (1998).  Numb-associated kinase interacts with the phosphotyrosine binding domain of Numb and antagonizes the function of Numb in vivo.  Mol. Cell. Biol. 18: 598-607.  [PDF]

  27. Lu, B., Jan, L.Y. and Jan, Y.N. (1998).  Asymmetric cell division: lessons from flies and worms.  Curr. Opin Genet. Dev. 8:392-399.  [PubMed]

  28. Jan, Y.N. and Jan, L.Y. (1998).  Asymmetric Cell Division.  Nature, 392:775-778.  [PubMed]

  29. Knoblich, J.A., Jan, L.Y. and Jan, Y.N. (1997).  Asymmetric Segregation of the Drosophila Numb Protein during Mitosis: Facts and Speculations.  Cold Spring Harbor Symposia on Quantitative Biology, LXII:71-77.  [PubMed]

  30. Wang, S., Younger-Shepherd, S., Jan, L.Y. and Jan, Y.N. (1997).  Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless.  Development 124:4435-4446.  [PDF]

  31. Knoblich, J.A., Jan, L.Y. and Jan, Y.N. (1997).  The N terminus of the Drosophila Numb protein directs membrane association and actin-dependent asymmetric localization.  Proc. Natl. Acad. Sci. USA 94:13005-13010.  [PDF]

  32. Shen, C.P., Jan, L.Y. and Jan, Y.N. (1997).  Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila.  Cell 90:449-458.  [PubMed]

  33. Frise, E., Knoblich, J.A., Younger-Shepherd, S., Jan, L.Y. and Jan, Y.N. (1996).  The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage.  Proc. Natl. Acad. Sci. USA 93:11925-11932.  [PDF]

  34. Kraut, R., Chia, W., Jan, L.Y., Jan, Y.N. and Knoblich, J.A. (1996).  Role of inscuteable in orienting asymmetric cell divisions in Drosophila.  Nature 383:50-55.  [PubMed]

  35. Guo, M., Jan, L.Y. and Jan, Y.N. (1996).  Control of daughter cell fates during asymmetric division; interaction of Numb and Notch.  Neuron 17:27-41.  [PubMed]

  36. Jan, Y.N. and Jan, L.Y. (1995).  Maggot's hair and bug's eye: role of cell interactions and intrinsic factors in cell fate specification.  Neuron 14:1-5.  [PubMed]

  37. Knoblich, J.A., Jan, L.Y. and Jan, Y.N. (1995).  Asymmetric segregation of Numb and Prospero during cell division.  Nature 377:624-627.  [PubMed]

  38. Guo, M., Bier, E., Jan, L.Y. and Jan, Y.N. (1995).  tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS.  Neuron 14:913-925.  [PubMed]

  39. Rhyu, M.S., Jan, L.Y. and Jan, Y.N. (1994).  Asymmetric distribution of numb protein during division of the Sensory Organ Precursor cell confers distinct fates to daughter cells.  Cell 76:477-491.  [PubMed]

  40. Vaessin, H., Grell, E., Wolff, E., Bier, E., Jan, L.Y. and Jan, Y.N. (1991).  prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila.  Cell 67: 941-953.  [PubMed]

  41. Bodmer, R., Carretto, R. and Jan, Y.N. (1989).  Neurogenesis of the Peripheral Nervous System in Drosophila Embryos: DNA replication Patterns and Cell lineages.  Neuron 3:21-32.  [PubMed]

  42. Uemura, T., Shepherd, S., Ackerman, L., Jan, L.Y. and Jan, Y.N. (1989).  numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryo.  Cell 58:349-360.  [PubMed]

Oogenesis and pole cell development

  1. Abdelilah-Seyfried, S., Cox, D.N., and Jan, Y.N. (2003).  Bazooka is a permissive factor for the invasive behavior of Discs large tumor cells in Drosophila ovarian follicular epithelia.  Development 130:1927-1935.  [PDF]

  2. Cox, D.N., Abdelilah Seyfried, S., Jan, L.Y. and Jan, Y.N. (2001).  Bazooka and atypical protein kinase C are required to regulate oocyte differenation in the Drosophila ovary.  Proc. Natl. Acad. Sci USA 98:14475-14480.  [PDF]

  3. Cox, D.N., Lu, B.-W., Sun, T.-Q., Williams, L.T., and Jan, Y.N. (2001).  Drosophila par-1 is required for oocyte differentiation and microtubule organization.  Curr. Biol. 11:75-87.  [PubMed]

  4. Roegiers, F. and Jan, Y.N. (2000).  Staufen: a common component of mRNA transport in oocytes and neurons?  Trends Cell Biol. 10: 220-224.  [PubMed]

  5. Clark, I.E., Jan, L.Y. and Jan, Y.N. (1997).  Reciprocal localization of nod and kinesin fusion proteins indicates microtubule polarity in Drosophila oocyte, epithelium, neuron and muscle.  Development 124:461-470.  [PDF]

  6. Jongens, T.A., Ackerman, L.D., Swedlow, J.R., Jan, L.Y. and Jan, Y.N. (1994).  Germ cell-less encodes a cell type-specific nuclear pore-associated protein and functions early in the germ-cell specification pathway of Drosophila.  Genes Dev. 8:2123-2136.  [PubMed]

  7. Clark, I., Giniger, E., Ruohola-Baker, H., Jan, L.Y. and Jan, Y.N. (1994).  Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte.  Curr. Biol. 4:289-300.  [PubMed]

  8. Ruohola-Baker, H., Jan, L.Y. and Jan, Y.N. (1994).  The role of gene cassettes in axis formation during Drosophila oogenesis.  Trends Genet. 10:89-94.  [PubMed]

  9. Siegel, V., Jongens, T.A., Jan, L.Y. and Jan, Y.N. (1993).  pipsqueak, an early acting member of the posterior group of genes, affects vasa level and germ cell-somatic cell interaction in the developing egg chamber.  Development 119:1187-1202.  [PDF]

  10. Theurkauf, W.E., Alberts, B.M., Jan, Y.N. and Jongens, T.A. (1993).  A central role for microtubules in the differentiation of Drosophila oocytes.  Development 118:1169-1180.  [PDF]

  11. Ruohola-Baker, H., Grell, E., Chou, T.B., Baker, D., Jan, L.Y. and Jan, Y.N. (1993).  Spatially localized Rhomboid is required for establishment of the dorsal-ventral axis in Drosophila oogenesis.  Cell 73:953-965.  [PubMed]

  12. Jongens, T.A., Hay, B., Jan, L.Y. and Jan, Y.N. (1992).  The germ cell-less gene product: A posteriorly localized component necessary for germ cell development in Drosophila.  Cell 70:569-584.  [PubMed]

  13. Ruohola, H., Bremer, K.A., Baker, D., Swedlowe, J.R., Jan, L.Y. and Jan, Y.N. (1991).  Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila.  Cell 66:433-449.  [PubMed]

  14. Hay, B., Jan, L.Y. and Jan, Y.N. (1990). Localization of vasa, a component of Drosophila polar granules, in maternal effect mutants that alter embryonic anteroposterior polarity.  Development 109:425-433.  [PubMed]

  15. Hay, B., Jan, L.Y. and Jan, Y.N. (1988).  A protein component of Drosophila polar granules is encoded by vasa and has extensive sequence similarity to ATP-dependent helicases.  Cell 55:577-587.  [PubMed]

  16. Hay, B., Ackerman, L., Barbel, S., Jan, L.Y. and Jan, Y.N. (1988).  Identification of a component of Drosophila polar granules.  Development 103: 625-640.  [PubMed]

Genomics

  1. McCarroll, S.A., Murphy, C.T., Zou, S., Pletcher, S.D., Chin, C.-S., Jan, Y.N., Kenyon, C., Bargmann, C.I. and Li, H. (2004). Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nature Genetics 36:197-204.  [PubMed]

  2. Zou, S., Meadows, S., Sharp, L., Jan, L.Y. and Jan, Y.N. (2000).  Genome-wide study of aging and oxidative stress response in Drosophila melanogaster.  Proc. Natl. Acad. Sci. USA 97: 13726-13731.  [PDF]

  3. Moore, A.W., Barbel, S., Jan, L.Y. and Jan, Y.N. (2000).  A genomewide survey of basic helix-loop-helix factors in Drosophila.  Proc. Natl. Acad. Sci. USA 97: 10436-10441.  [PDF]

Vertebrate homologs

  1. Anderson, A.C., Kitchens, E.A., Chan, S.W., Hill, C. St., Jan, Y.N., Zhong, W., and Robey, E.A. (2005). The Notch regulator numb links the Notch and TCR signaling pathways. J. Immunol. 174:890-897.  [PubMed]

  2. Huang, E.J., Li, H.h., Tang, A.A., Wiggins, A.K., Neve, R.L., Zhong, W., Jan, L.Y. and Jan, Y.N. (2005). Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization. Genes Dev. 19:138-151.  [PubMed]

  3. Shi, S.-H., Cheng, T., Jan, L.Y., and Jan, Y.N. (2004). APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr. Biol. 14:2025-2032.  [PubMed]

  4. Shi, S.-H., Cox, D.N., Wang, D., Jan, L.Y., and Jan, Y.N. (2004). Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1). Proc. Natl. Acad. Sci. USA 101:13341-13345.  [PubMed]

  5. Shi, S.-H., Cheng, T., Jan, L.Y., and Jan, Y.N. (2004). The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation. Proc. Natl. Acad. Sci. USA 101:13346-13351.  [PDF]

  6. Li, H.-S., Wang, D., Shen, Q., Schonemann, M.D., Gorski, J.A., Jones, K.R., Temple, S., Jan, L.Y., and Jan, Y.N. (2003). Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron 40:1105-1118.  [PubMed]

  7. Shi, S.-H., Jan, L.Y., and Jan, Y.-N. (2003)  Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity.  Cell 112:63-75.  [PubMed]

  8. Petersen, P.H., Zou, K., Hwang, J.K., Jan, Y.N., and Zhong, W. (2002)  Progenitor cell maintenance requires numb and numblike during mouse neurogenesis.  Nature 419:929-934.  [PubMed]

  9. Donovan, J., Kordylewska, A., Jan, Y., and Utset, M. (2002)  Tetralogy of fallot and other congenital heart defects in Hey2 mutant mice.  Curr. Biol. 12:1605-1610.  [PubMed]

  10. Shen, Q., Zhong, W., Jan, Y.N., and Temple, S. (2002).  Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts.  Development 129:4843-4853.  [PDF]

  11. Horne-Badovinac, S., Lin, D., Waldron, S., Schwarz, M., Mbamalu, G., Pawson, T., Jan, Y.-N., Stainier, D.Y.R. and Abdelilah-Seyfried, S. (2001).  Positional cloning of heart and soul reveals multiple roles for PKCλ in zebrafish organogenesis.  Curr. Biol. 11:1492-1502.  [PubMed]

  12. Ruan, Y., Tecott, L., Jiang, M.-M., Jan, L.Y., and Jan, Y.N. (2001).  Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized.  Proc. Natl. Acad. Sci. USA 98: 9907-9912.  [PDF]

  13. Zhong, W., Jiang, M.-M., Schonemann, M.D., Meneses, J.J., Pedersen, R.A., Jan, L.Y., and Jan, Y.N. (2000).  Mouse numb is an essential gene involved in cortical neurogenesis.  Proc. Natl. Acad. Sci. 97:6844-6849.  [PDF]

  14. Kanekar, S., Perron, M., Dorsky, R., Harris, W.A., Jan, L.Y., Jan, Y.N. and Vetter, M.L. (1997).  Xath5 participates in a network of bHLH genes in the developing Xenopus retina.  Neuron 19:981-994.  [PubMed]

  15. Zhong, W., Jiang, M.M., Weinmaster, G., Jan, L. Y., and Jan, Y. N. (1997).  Differential expression of mammalian Numb, Numblike and Notch1 suggest distinct roles during mouse cortical neurogenesis.  Development 124:1887-1897.  [PDF]

  16. Zhong, W., Feder, J.N., Jiang, M.M., Jan, L.Y. and Jan, Y.N. (1996).  Asymmetric localization of a mammalian Numb homologue during mouse cortical neurogenesis.  Neuron 17:43-53.  [PubMed]

  17. Feder, J.N., Li, L., Jan, L.Y. and Jan, Y.N. (1994).  Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene hairy.  Genomics 20:56-61.  [PubMed]

  18. Feder, J.N., Jan, L.Y. and Jan, Y.N. (1993).  A rat gene with sequence homology to the Drosophila gene hairy is rapidly induced by growth factors known to influence neuronal differentiation.  Mol. Cell Biol. 13:105-113.  [PDF]

Miscellaneous (Pontifications)

  1. Yuh-Nung Jan (2003). Q & A. Curr. Biol. 13:R378-R379  [PubMed]

  2. Jan, Y.N. (2000).  Curious Seymour (Book Review).  Cell 101: 123-125.  

  3. Jan, Y.N. and Jan, L.Y. (2000).  Humble starts and conserved themes in neurogenetic studies.  Harvey Lecture 94: 21-45.  [PubMed]

  4. Jan, Y.N. and Jan, L.Y. (1998).  Serendipity, the principle of limited sloppiness, and neural development.  Int. J. Dev. Biol. 42:531-533.  [PubMed]

  5. Jan, Y.N. (1997).  Pre-empting the arrival of a dark lord (correspondence).  Nature 389:665.  [PubMed]

  6. Jan, Y.N. and Jan, L.Y. (1990).  In Rememberance of Stephen W. Kuffler, ed. U.J. McMahan, pp. 47-50.  Sinauer Inc., Sunderland, MA.  

他们夫妇二人培养出的知名科学家列表（Associate Professor以上）：

Bruce Tempel：Professor, University of Washington, Seattle
Tom Schwarz：Professor, Harvard Medical School/Children’s Hospital
Diane Papazian：Professor, UCLA
Ethan Bier：Professor, UC San Diego
Gabrielle Boulianne：Senior Scientist , University of Toronto, Hospital for Sick Children
Yi Rao： Professor, Northwestern University
Ehud Isacoff： Professor, University of California Berkeley
Meei–Ling Tsaur： Associate Professor, National Yang–Ming University
Morgan Sheng： Professor, HHMI Associate Investigator, MIT
Liqun Luo（骆利群）： Associate Professor, HHMI investigator, Stanford University
Michael Brand： Group Leader, Max Planck Institute, Dresden
Yoshihiro Kubo： Professor, National Institute for Physiological Sciences, Japan
Min Li ： Associate Professor, Johns Hopkins Medical School
Ed Giniger： Investigator, NINDS, NIH
Hannele Ruohola–Baker： Associate Professor, University of Washington, Seattle
Tom Jongens： Associate Professor, University of Pennsylvania
Harald Vaessin： Associate Professor, Ohio State University
Michael Caudy：Associate Professor, Cornell University
Tadashi Uemura：Professor, Kyoto University
Rolf Bodmer：Professor, The Burnham Institute
Heidi Phillips： Senior Scientist, Genentech
Flora Katz： Associate Professor, Texas A & M University
Dale Branton：Associate Professor, University of Minnesota
Bruce Hay： Associate Professor, Cal Tech
Chou–Long Huang： Associate Professor, University of Texas South Western Medical School
Eitan Reuveny： Associate Professor, Weizmann Institute

研究兴趣与方向

Research Summary

We are interested in the basic mechanisms of neural development. Our strategy is to take a relatively simple nervous system, the Drosophila peripheral nervous system, and try to discover the genetic program that controls its development. In doing so, we hope to uncover evolutionarily conserved core programs that control different steps of neural development in animals. We started with the earliest steps in neural development (neurogenesis and neuronal cell fate specification) and gradually worked our way toward later steps (differentiation aspects such as neuronal morphogenesis and neuronal functions). Some highlights of our earlier efforts include the finding of atonal and numb. Functioning as a proneural gene, atonal initiates the development of two major types of sensory neurons: the chordotonal neuron and the founding photoreceptor R8. The study of atonal led to the notion that different proneural genes are important for the development of different neurons. During asymmetric cell division, numb functions as a cell fate determinant. Numb provided a starting point for the study of asymmetric cell division in Drosophila and vertebrates, which led to considerable insight into the molecular basis of asymmetric cell division. Although we are continuing with the study of asymmetric cell division, the major focus of our lab has recently shifted to the study of neuronal morphogenesis, particularly dendrite development.

Genetic Control of Dendrite Development in Drosophila

The nervous system is composed of a vast number of neurons with strikingly different dendritic morphology. Neurons are highly polarized cells with distinct subcellular compartments, including one or multiple dendritic processes and a single, extended axon. For a nervous system to be wired correctly, the axons have to be guided toward the correct targets and the dendrites need to have the correct branching pattern. At present, much less is known about the molecular mechanisms that control the dendrite branching pattern than the mechanisms that control axon guidance. To use Drosophila genetics to identify core programs that control dendrite development, we developed a simple assay system. We use the fly transgenic technique to express green fluorescent protein (GFP) in the dendritic arborization (da) neurons, a group of sensory neurons with a stereotyped dendritic branching pattern. This allows us to visualize the development of the dendrites of da neurons in the living fly embryos and to use them as an assay system for a genetic dissection of dendrite development. We have begun to break down dendrite development into a set of smaller and more manageable problems.

1. What genetic program distinguishes neurons with single dendrites from the ones with multiple dendrites? Once a neuron starts differentiation, it usually elaborates a single axon. In contrast, the number of dendrites and the extent of branching for different neurons vary greatly, depending on neuronal type. How is it that one neuron has a single unbranched dendrite whereas its neighbor can have a very extensive branching pattern? Insight came from our recent screen for dendritic mutants that led to the discovery of a gene called hamlet. The hamlet gene encodes a multiple-domain, evolutionarily conserved, zinc finger containing nuclear protein that is transiently expressed in a subset of neurons at the time of dendrite outgrowth. We found that hamlet functions as a binary genetic switch for the elaboration of dendritic arbors in sensory neurons.

2. How do different classes of neurons acquire their distinctive, class-specific dendritic morphology? Functionally similar neurons often share common dendrite morphology, but how neurons of each class are directed into class-specific forms is not understood. The da neurons can be divided into four classes. Class I and II have a relatively simple dendritic branching pattern and small dendritic field. In contrast, class III and IV neurons have a more complex dendritic branching pattern and large dendritic field. We found that these four classes of neurons express four distinct levels of Cut, a homeodomain containing transcriptional factor. Class I, II, IV, and III neurons have nondetectable, low, medium, and high levels of Cut expression, respectively, throughout embryonic and larval development. By analyzing loss-of-function mutations and class-specific overexpression of Cut, we demonstrated that indeed the level of Cut expression controls the distinct, class-specific patterns of dendritic branching. Remarkably, a human Cut homolog, CDP, can substitute for Drosophila Cut in promoting the dendritic morphology of high-Cut neurons. Thus, Cut may function as an evolutionarily conserved regulator of distinct, neuronal-type-specific dendrite morphology.

3. What are the roles of local translation and its molecular components in dendrite development? There is increasingly strong evidence that local protein synthesis and translational control play important roles in dendrite morphogenesis and synaptic plasticity. The molecular components of translational control necessary for dendritic morphogenesis remain largely unknown, however. Recently, we discovered that nanos and pumilio are essential for proper morphogenesis of higher order dendritic branches of the da neurons. Furthermore, Nanos is localized to the RNA granules in the dendrites of da neurons. Our results suggest that the Nanos/Pumilio translational repression complex functions locally at the dendrite to regulate the morphogenesis of higher order dendritic branches.

4. What is the underlying molecular mechanism for tiling? Dendritic tiling, a complete but nonredundant coverage of a receptive field by dendrites of functionally homologous neurons, was first described in mammalian retina. We found that class III and class IV (but not class I or class II) da neurons exhibit tiling. Tiling appears to be a general organizing principle in the nervous system, but the mechanism is largely unknown. Recently, we found the first tiling mutants in fly. Two fly genes, furry (fry) and tricornered (trc), that were previously characterized for other functions, are required for proper tiling. In wild type, the dendrites of neighboring da neurons of the same class almost never cross over. In mutants, there are many examples of crossing-over. The fry gene functions as a positive regulator of the trc kinase. Both genes were originally identified and cloned in Paul Adler's lab (University of Virginia, Charlottesville) because the mutants affect hair morphology. Each gene belongs to an evolutionarily conserved family. They function together to regulate cellular morphology in organisms ranging from fungi to worm, fly, and possibly vertebrates. Trc and Fry provide us with an entry point to identify the signal transduction pathway underlying tiling.

Dendrite Development of Mammalian Central Neurons

1. How do neurons acquire their axon vs. dendrite polarity? An attractive hypothesis is that neuronal polarity is controlled by some of the same molecular cues for epithelial polarity. By using dissociated rat hippocampal neuron culture, we showed that the mammalian homologs mPar3, mPar6, and mAPKC (atypical PKC) indeed play critical roles in controlling neuronal polarity. We further demonstrated that the mPar3 complex acts downstream of phosphatidylinositol 3-kinase in specifying neuronal polarity. It thus appears that cultured hippocampal neurons specify their axons via a pathway involving a cascade of kinases as well as the polarized distribution of molecules that are evolutionarily conserved for their ability to polarize cells.

2. Dasm1 (dendrite arborization and synapse maturation 1), a mammalian member of a novel immunoglobulin superfamily, is required for dendrite arborization and synapse maturation of hippocampal neurons. Having found that the gene turtle is a regulator of dendrite arborization in Drosophila, we extended the finding to the mammalian central nervous system by cloning its mammalian homolog, Dasm1, which is highly expressed in the developing brain and localized at the dendrites and synapses. Suppression of Dasm1 expression in hippocampal neurons at early stages specifically impairs dendrite, but not axon, outgrowth. Dasm1 also promotes synapse maturation in later stage hippocampal neurons by regulating synaptic AMPA receptors. Dasm1 defines a new family of molecules likely involved specifically in dendrite outgrowth and synapse formation.

Grants from the National Institutes of Health provided partial support for our research.

 

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