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Modeling polarity buildup and cell fate decision in the fly eye: insight into the connection between the PCP and Notch pathways

机译:苍蝇眼中的极性建立和细胞命运决定建模:洞悉PCP和Notch通路之间的联系

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Metazoan development critically depends on a surprisingly short list of conserved pathways. How can such ubiquitous systems regulate a variety of cell-biological events at various developmental stages in different tissues and in different organisms? In the fruit fly, the planar cell polarity (PCP) pathway regulates widely different processes. It is known to be involved in the correct alignment of hairs on the wing and in the determination of R3/R4 photoreceptor cell fates in the eye. In the wing, PCP regulates the spatial structure of cells sharing the same transcriptional fate, while in the eye the Notch signaling pathway has been recruited to additionally transduce the PCP signal to the nuclei in the two differentiating members of a photoreceptor pair. We have recently proposed a computational model for PCP in the wing; this model posited, on the basis of all known data, that planar polarity buildup is driven by asymmetric molecular complexes constructed around the cadherin Flamingo and spanning the space between two cells. In this paper, we show that the same model, combined with a novel Notch module, equally applies in the eye. The model provides insight into the crosstalk between the PCP and Notch modules in development and illustrates the ability of signaling modules to robustly maintain vital phenotypes in a noisy environment.
机译:后生动物的发育关键取决于保守途径的出乎意料的简短。这种无处不在的系统如何在不同组织和不同生物体的不同发育阶段调节各种细胞生物学事件?在果蝇中,平面细胞极性(PCP)途径调节着广泛不同的过程。已知与机翼上毛发的正确排列以及眼睛中R3 / R4感光细胞命运的确定有关。在机翼中,PCP调节共享相同转录命运的细胞的空间结构,而在眼睛中,Notch信号通路已被招募,以将PCP信号另外转导至光感受器对的两个区分成员中的核。我们最近提出了机翼PCP的计算模型。根据所有已知数据,该模型假设平面极性的建立是由围绕钙粘蛋白火烈鸟构建并跨越两个细胞之间空间的不对称分子复合物驱动的。在本文中,我们证明了相同的模型与新颖的Notch模块相结合,同样适用于眼睛。该模型提供了对正在开发的PCP和Notch模块之间的串扰的洞察力,并说明了信号模块在嘈杂的环境中稳健地维持重要表型的能力。

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