The spatiotemporal order of signaling events unveils the logic of development signaling.
The spatiotemporal order of signaling events unveils the logic of development signaling.
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DOI：
10.1093/bioinformatics/btw121
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Mao Y
中科院分区：
文献类型：
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作者：
Zhu H;Owen MR;Mao Y
动机：从蠕虫和昆虫到鸟类和哺乳动物的动物都显示出不同的身体计划;然而，具有组织和器官的不同身体计划的胚胎发育由令人惊讶的少数信号通路控制。众所周知，信号通路的组合使用和动态相互作用遵循特定的逻辑来控制复杂和准确的发育信号和模式，但这种逻辑是什么，甚至看起来像什么，仍然是难以捉摸的。结果如下：我们已经开发了一个果蝇眼睛发育的计算模型与创新的方法来揭示多个途径之间的相互作用如何控制动态生成的六边形阵列的R8细胞。我们获得了两个新的发现。首先，由前神经Hh信号传导产生的长程诱导信号与由抗神经Notch和EGFR信号传导产生的短程限制信号之间的耦合对于产生精确间隔的R8至关重要。其次，关键信号传导事件的时空顺序揭示了由Ato协调的Notch和EGFR信号传导进行的侧向抑制的稳健模式，以共同确定R8模式。这种模式规定了信号的顺序，并与通信协议相媲美，可能有助于破译备受赞赏但定义不清的发育信号逻辑。可用性和实施：该模型可应要求提供。联系人：hao. ymail.com补充信息：补充数据可在生物信息学在线获得。
Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling. Availability and implementation: The model is available upon request. Contact: hao.zhu@ymail.com Supplementary information: Supplementary data are available at Bioinformatics online.