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

Modeling polarity buildup and cell fate decision in the fly eye: insight into the connection between the PCP and Notch pathways
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DOI:
10.1007/s00427-008-0235-y
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发表时间:
2008-08-01
影响因子:
2.4
通讯作者:
Kerszberg, Michel
Kerszberg, Michel
中科院分区:
生物学4区
文献类型:
--
作者:
Le Garrec, Jean-Francois;Kerszberg, Michel

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后生动物的发育主要依赖于一份短得惊人的保守通路清单。这些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)通路调节着广泛不同的过程。众所周知,它与翅膀上毛发的正确排列和眼睛中R3/R4感光细胞命运的决定有关。在翅膀中,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信号通路已被招募来额外地将PCP信号转导到一对光感受器的两个分化成员的细胞核中。我们最近提出了机翼PCP的计算模型;该模型在所有已知数据的基础上假设,平面极性的形成是由围绕火烈鸟钙粘蛋白构建的不对称分子复合物驱动的,这些分子复合物横跨两个细胞之间的空间。在本文中,我们证明了同样的模型,结合一个新的Notch模块,同样适用于眼睛。该模型提供了PCP和Notch模块在发育过程中的串扰,并说明了信号模块在嘈杂环境中稳定维持重要表型的能力。
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.