A Genetic Network Conferring Canalization to a Bistable Patterning System in Drosophila
A Genetic Network Conferring Canalization to a Bistable Patterning System in Drosophila
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DOI：
10.1016/j.cub.2013.09.055
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发表时间：
2013-11-18
期刊：
影响因子：
9.2
通讯作者：
Ferguson, Edwin L.
中科院分区：
文献类型：
--
作者：
Gavin-Smyth, Jackie;Wang, Yu-Chiun;Ferguson, Edwin L.
为了实现“野生型的恒定性”，发育中的生物体必须对随机波动和环境扰动进行缓冲[1]。理论上，这种表型缓冲是由各种遗传机制引起的[2]，并且被广泛认为是适应性的，对生存力至关重要。在果蝇胚盘胚胎中，用抗骨形态发生蛋白（BMP）信号转导子Mad、pMad的活性磷酸化形式的抗体染色[3，4]，或BMP-受体相互作用空间模式的可视化[5]揭示了以背中线为中心的BMP信号传导空间模式。该信号传导事件对于背侧细胞命运的特化是必不可少的，包括胚外浆膜[5-7]。BMP信号传导由促进的细胞外扩散启动[4，8]，其将BMP配体定位于背部。BMP信号传导然后激活促进未来BMP-受体相互作用的细胞内正反馈回路[5，6]。在这里，我们确定了一个遗传网络，包括三个基因，canalizes这个BMP信号事件。BMP靶标eiger（Eiger）在正反馈回路中起作用以促进信号传导，而由crossveinless-2（cv-2）编码的BMP结合蛋白拮抗信号传导。这两种基因的表达都需要同源异型盒基因zerknullt（zen）的早期活性。两种缺乏早期zen表达的果蝇物种在BMP信号传导中具有高变异性。这些数据都详细说明了一个新的机制，产生发展渠道，并确定一个物种与noncanalized轴向图案的例子。
To achieve the "constancy of the wild-type," the developing organism must be buffered against stochastic fluctuations and environmental perturbations [1]. This phenotypic buffering has been theorized to arise from a variety of genetic mechanisms [2] and is widely thought to be adaptive and essential for viability. In the Drosophila blastoderm embryo, staining with antibodies against the active, phosphorylated form of the bone morphogenetic protein (BMP) signal transducer Mad, pMad [3, 4], or visualization of the spatial pattern of BMP-receptor interactions [5] reveals a spatially bistable pattern of BMP signaling centered on the dorsal midline. This signaling event is essential for the specification of dorsal cell fates, including the extraembryonic amnioserosa [5-7]. BMP signaling is initiated by facilitated extracellular diffusion [4, 8] that localizes BMP ligands dorsally. BMP signaling then activates an intracellular positive feedback circuit that promotes future BMP-receptor interactions [5, 6]. Here, we identify a genetic network comprising three genes that canalizes this BMP signaling event. The BMP target eiger(egr) acts in the positive feedback circuit to promote signaling, while the BMP binding protein encoded by crossveinless-2 (cv-2) antagonizes signaling. Expression of both genes requires the early activity of the homeobox gene zerknullt (zen). Two Drosophila species lacking early zen expression have high variability in BMP signaling. These data both detail a new mechanism that generates developmental canalization and identify an example of a species with noncanalized axial patterning.