Size matters: The contribution of cell proliferation to the progression of the specification Drosophila eye gene regulatory network
Size matters: The contribution of cell proliferation to the progression of the specification Drosophila eye gene regulatory network
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DOI：
10.1016/j.ydbio.2010.06.015
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发表时间：
2010-08-15
影响因子：
2.7
通讯作者：
Casares, Fernando
中科院分区：
文献类型：
--
作者：
Amore, Gabriele;Casares, Fernando
器官发育是一个复杂的过程，其中许多相互作用的转录因子和信号通路的活性需要与增殖生长相结合。发育基因调控网络（GRNs）允许在系统水平上捕获必要的调控途径，并提供了一种有效的方法来接近这种复杂性。然而，典型的GRNs研究集中在非常早期的胚胎阶段（通常是原肠胚形成前）或晚期阶段，此时几乎没有或没有细胞增殖，因此不考虑器官生长如何整合在发育过程中。这可以方便地调查在果蝇眼原基。在这里，我们提出了一个工作模型，旨在说明如何在一个关键时期，第二个幼虫阶段，细胞的增殖模式的变化是协调的视网膜决定（RD）基因程序的启动。这种变化是受两种不同的信号源（Wnt 1/wg和BMP 2/4/dpp）的调节，分别由原基的前端和后端产生。dpp信令是触发RD程序所必需的。然而，为了使其有效，接收Dpp的小区必须在wg信令范围之外。这是由于RD表达开始之前的增殖性生长而获得的。通过这个网络模型，许多先前已知参与生长和模式化的基因调控步骤被联系起来。对该模型的分析突出了一些基本的监管原则，并提出了新的问题。此外，这些原则可能在其他器官的生长和模式化过程中起作用。(C)2010年爱思唯尔公司All rights reserved.
Organ development is a complex process in which the activity of scores of interacting transcription factors and signaling pathways need to be integrated with proliferative growth. Developmental gene regulatory networks (GRNs) allow capturing essential regulatory pathways at a systems-level and provide an effective way of approaching such complexity. However typical GRNs studies focus on very early embryonic stages (usually pre-gastrulation) or late stages, when there is little or no cell proliferation, and therefore do not consider how organ growth is integrated in the developmental process. This can be conveniently investigated in the Drosophila melanogaster eye primordium.Here we present a working model meant to illustrate how during a critical period, the second larval stage, changes in cells' proliferative pattern are coordinated with the initiation of the Retinal Determination (RD) gene program. Such changes are regulated in response to two different sources of signal (Wnt1/wg and BMP2/4/dpp) produced by the anterior and posterior ends of the primordium, respectively. The dpp signaling is necessary to trigger the RD program. However in order for it to be effective, cells receiving Dpp have to be out of the wg signaling range. This is obtained thanks to the proliferative growth that precedes the onset of RD expression. With this network model many of the gene regulatory steps previously known to participate in growth and patterning are linked. Analysis of the model highlights a few essential regulatory principles, as well as poses new questions. In addition, these principles might operate during the growth and patterning of other organs. (C) 2010 Elsevier Inc. All rights reserved.