Steven Beckendorf
Steven BeckendorfProfessor of Genetics and DevelopmentE-mail: beckendo@berkeley.edu |
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Full Directory InformationResearch Interests
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We are interested in the genetic mechanisms which establish distinct tissues and organs during development, including both the initial instructions that define an organ and the subsequent cell-cell signaling, changes in gene expression, and cellular movements that build the differentiated organ. We are currently focussing on two specific areas: the regulatory pathways in Drosophila embryos that define the salivary gland primordium and initiate its morphogenesis, and a novel tyrosine kinase signaling pathway necessary for ring canal growth during Drosophila oogenesis.
Current Projects
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Salivary gland development We have chosen to study the development of an apparently simple organ, the salivary gland of Drosophila embryos, with the hope of characterizing the entire genetic pathway which controls its determination and morphogenesis. Because each gland is assembled from a small number of cells (about 100), because the glands are the first functional organs to form in the embryo, and because we can examine the genetic control of both their determination and morphogenesis, we can use salivary gland development to address many important questions about organogenesis.
The salivary glands develop from the ventral epidermis of a single embryonic segment. We have shown that the salivary primordium is initially specified by the homeotic gene Sex combs reduced (Scr) which induces the transcription of all early salivary-specific genes. The primordium is then divided into pregland and preduct cells by signaling from the ventral midline via the EGF receptor pathway. This signal restricts the FORK HEAD transcription factor to the pregland cells and the TRACHEALESS transcription factor to the preduct cells. A third transcription factor, EYE GONE is restricted to a few posterior pregland cells and the posterior half of the preduct cells. As a result of their overlapping domains of expression, these three transcriptional regulators define the fate of four distinct regions of the salivary glands.
After the fate of the cells is determined, morphogenesis begins. The primordium invaginates into the interior of the embryo in a complex and coordinated process to form tubular salivary glands that are connected to the pharynx by Y-shaped tubular ducts. Cells in the four defined regions invaginate by at least three different mechanisms, apparently specified by combinations of the three transcriptional regulators. We now want to investigate how genes downstream from these transcription factors direct the changes in cell shape that accompany these complex cell rearrangements and how the rearrangements are coordinated so that a continuous lumen links cells invaginatedby different mechanisms. We have initiated a variety of genetic and molecular screens to identify downstream genes and to determine their roles in salivary morphogenesis.
Oogenesis and the Tec29 tyrosine kinase. During oogenesis in Drosophila, the growth of the oocyte as well as the determination of its dorsoventral and anteroposterior axes relies on gene products made in the adjacent nurse cells. These nurse cell gene products are transferred to the oocyte through cytoplasmic bridges known as ring canals. The ring canals are dynamic structures that increase in diameter more than ten-fold during oogenesis by the addition of large amounts of filamentous actin and the slippage of preexisting actin filaments past each other. We have shown that the TEC29 tyrosine kinase is localized to the ring canals and regulates their growth. We have begun to define a TEC29 signaling pathway by showing that a second tyrosine kinase, SRC64, is required for TEC29 localization to the ring canals and that both proteins are required for tyrosine phosphorylation of ring canal proteins. These are intriguing results because mammalian SRC and TEC family kinases have been shown to interact and to regulate cytoskeletal organization. The rest of the signaling pathway is, however, largely undefined. We are now using both genetic and physical interaction screens to identify other members in this pathway, especially the downstream targets that interact with the actin cytoskeleton.
Selected Publications
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Salivary gland determination in Drosophila: dissection of a salivary-specific, fork head enhancer reveals multiple interacting genetic pathways. [B. Zhou, A. Bagri, and S. K. Beckendorf (2001) Developmental Biology 237, 54-67]
The Drosophila Pax gene eye gone is required for embryonic salivary duct development. [N. A. Jones, Y. M. Kuo, Y. H. Sun, and S. K. Beckendorf (1998) Development 125, 4163-4174]
The Tec29 tyrosine kinase is required during Drosophila embryogenesis and interacts with Src64 in ring canal development. [E. M. Roulier, S. Panzer and S. K. Beckendorf (1998) Molecular Cell 1, 819-829]
Salivary duct determination in Drosophila: roles of the EGF receptor signaling pathway and the transcription factors Fork head and Trachealess. [Y. M. Kuo, N. Jones, B. Zhou, S. Panzer, V. Larson, and S. K. Beckendorf (1996) Development 122, 1909-1917]
The Broad-Complex directly controls a tissue specific response to the steroid hormone ecdysone at the onset of metamorphosis. [L. von Kalm, K. Crossgrove, D. Von Seggern, G. M. Guild, and S. K. Beckendorf (1994)EMBO J. 13, 3505-3516]
A transcriptional switch between the Pig-1 and Sgs-4 genes of Drosophila. [E. Mougneau, D. Von Seggern, T. Fowler, J. Rosenblatt, T. Jongens, B. Rogers, D. Gietzen, and S. K. Beckendorf (1993) Mol. Cell. Biol. 13, 184_195]
Organogenesis in Drosophila melanogaster: Control of embryonic salivary gland determination by homeotic and dorsoventral patterning genes. [S. Panzer, D. Weigel, and S. K. Beckendorf (1992) Development 114, 49_57]
Last Updated 9/2/2003
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