PLoS Biology：两个蛋白质控制大脑发育
生物谷报道：英国伦敦大学学院的科学家发现了两种分别叫做BERT和ERNI的蛋白质如何在胚胎中相互作用以控制身体中不同器官系统何时开始形成。这些发现深化了我们对大脑和神经系统发育的了解，并且扩展了我们对干细胞行为的了解。这项研究的结果发表在本周的开发杂志PLoS Biology上。
这项新研究解开了脊椎动物确定不同结构部分的发育先后情况。在发育过程中，只有一些信号指令细胞形成数千细胞型，因此细胞如何破译这些信号的时间至关重要。由Claudio Stern教授领导的一个国际研究组证实大脑和神经系统发育的第一阶段是阻碍它的发育进程！
研究人员描述了发生在脊椎动物胚胎中的一个反应的结果，这个反应发生在几个小时大的胚胎中，并且是一种发育定时机制，能临时防止神经细胞的发育。这种神经细胞将会形成大脑和神经系统。这个细胞的反应领先于胚胎中其他将要形成内部器官、皮肤的细胞，以防止免疫系统过早发育。
Costis Papanayotou博士发现一种叫做BERT的新蛋白与他们研究组发现的ERNI蛋白质相互结合，联合其他蛋白质解除对Sox2基因的抑制。这个基因是细胞开始形成大脑和神经系统的绿色指示灯。
Stern教授表示，研究人员一直在寻找决定胚胎中细胞何时行使特殊功能的开关。他们的研究表明，BERT和ERNI蛋白是一种对抗关系：BERT比较强势并且能够解除ERNI蛋白对Sox2基因的抑制，而这种基因对构建神经系统至关重要。由于Sox2基因还是干细胞得以在身体重起不同作用所必须得，因此这项研究还提升了我们对成人体内干细胞行为的知识。（生物谷）
生物谷推荐原始出处：
PLoS Biology
Received: May 8, 2007; Accepted: November 26, 2007; Published: January 8, 2008
A Mechanism Regulating the Onset of Sox2 Expression in the Embryonic Neural Plate
1 Department of Anatomy & Developmental Biology, University College London, London, United Kingdom, 2 Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Lyon, France, 3 Ecole Normale Supérieure de Lyon, CNRS/INRA, Lyon, France, 4 Wellcome/Cancer Research UK Gurdon Institute for Cancer and Developmental Biology, Cambridge, United Kingdom
In vertebrate embryos, the earliest definitive marker for the neural plate, which will give rise to the entire central nervous system, is the transcription factor Sox2. Although some of the extracellular signals that regulate neural plate fate have been identified, we know very little about the mechanisms controlling Sox2 expression and thus neural plate identity. Here, we use electroporation for gain- and loss-of-function in the chick embryo, in combination with bimolecular fluorescence complementation, two-hybrid screens, chromatin immunoprecipitation, and reporter assays to study protein interactions that regulate expression of N2, the earliest enhancer of Sox2 to be activated and which directs expression to the largest part of the neural plate. We show that interactions between three coiled-coil domain proteins (ERNI, Geminin, and BERT), the heterochromatin proteins HP1α and HP1γ acting as repressors, and the chromatin-remodeling enzyme Brm acting as activator control the N2 enhancer. We propose that this mechanism regulates the timing of Sox2 expression as part of the process of establishing neural plate identity.
Figure 2.Expression of HP1α during Normal Development
(A–C) Before and during gastrulation, HP1α is expressed throughout the embryo although its expression becomes gradually stronger in the prospective neural plate.
(D–I) At the end of gastrulation (D), HP1α expression in the ectoderm becomes restricted in the prospective neural plate, where it gets stronger in subsequent stages (E–I) while it disappears from the nonneural ectoderm and the extra-embryonic epiblast.
The number on each panel represents the embryonic stage according to Eyal-Giladi and Kochav [60] for pre-primitive streak stages (in Roman numerals), and Hamburger and Hamilton [7] for later stages (Arabic numerals).
全文链接：
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0060002
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