ojoplano-mediated basal constriction is essential for optic cup morphogenesis
ojoplano-mediated basal constriction is essential for optic cup morphogenesis
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DOI：
10.1242/dev.033563
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发表时间：
2009-07-01
期刊：
影响因子：
4.6
通讯作者：
Wittbrodt, Joachim
中科院分区：
文献类型：
--
作者：
Ramon Martinez-Morales, Juan;Rembold, Martina;Wittbrodt, Joachim
尽管脊椎动物视网膜是一个被充分研究的器官发生范例，但脊椎动物视杯结构的形态发生机制在很大程度上仍然未知。了解眼睛的半球形形状是如何形成的，需要解决个体细胞行为如何协调以指导上皮形态发生的基本问题。在这里，我们分析了ojoplano （opo）在上皮组织形态发生中的作用，该基因是一种未表征的基因，其人类同源性与口面部裂综合征有关。最值得注意的是，当opo在medaka鱼中突变时，视杯折叠受损。我们在体内表征视杯形态发生，并确定在细胞水平上opo如何影响这一过程。Opo编码一种发育调节的跨膜蛋白，该蛋白定位于分泌途径的室室和神经上皮前体的基底端足。我们发现，Opo调节聚焦黏附成分到基底细胞表面的极化定位。此外，整合素粘附功能的组织特异性干扰会损害视杯折叠，类似于在opo突变体中观察到的眼部表型。我们提出了一种视网膜形态发生模型，其中opo介导的焦点接触形成需要传递驱动脊椎动物光学杯宏观折叠的机械张力。
Although the vertebrate retina is a well-studied paradigm for organogenesis, the morphogenetic mechanisms that carve the architecture of the vertebrate optic cup remain largely unknown. Understanding how the hemispheric shape of an eye is formed requires addressing the fundamental problem of how individual cell behaviour is coordinated to direct epithelial morphogenesis. Here, we analyze the role of ojoplano (opo), an uncharacterized gene whose human ortholog is associated with orofacial clefting syndrome, in the morphogenesis of epithelial tissues. Most notably, when opo is mutated in medaka fish, optic cup folding is impaired. We characterize optic cup morphogenesis in vivo and determine at the cellular level how opo affects this process. opo encodes a developmentally regulated transmembrane protein that localizes to compartments of the secretory pathway and to basal end-feet of the neuroepithelial precursors. We show that Opo regulates the polarized localization of focal adhesion components to the basal cell surface. Furthermore, tissue-specific interference with integrin-adhesive function impairs optic cup folding, resembling the ocular phenotype observed in opo mutants. We propose a model of retinal morphogenesis whereby opo-mediated formation of focal contacts is required to transmit the mechanical tensions that drive the macroscopic folding of the vertebrate optic cup.