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Abstract：
The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1(UW1)) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1(UW1) mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis.
摘要：
脊椎动物的眼睛通过一系列复杂的形态发生事件形成。光学囊泡外溢并经历变形形状变化以形成光学杯，其中神经视网膜和视网膜色素上皮包裹晶状体。人们早就知道，一个复杂的，富含糖蛋白的细胞外基质层在整个过程中围绕着发育中的视杯，然而，基质的功能及其特定的分子成分仍不清楚。先前的工作确立了层粘连蛋白细胞外基质在眼睛发育的特定步骤中的作用，包括视神经囊泡外泄，晶状体分化，和视网膜神经节细胞极化，然而，目前还不清楚层粘连蛋白在视杯形成的早期过程中可能起什么作用。这里,我们使用斑马鱼lama1突变体（lama1（UW1））来确定层粘连蛋白在视杯形态发生过程中的功能。使用实时成像，我们发现,令人惊讶的是,层粘连蛋白的丢失以时空特异性方式导致对粘着斑组装的不同影响，层粘连蛋白是视杯形态发生的多个步骤所必需的，包括视神经柄收缩，内陷，和球面透镜的形成。层粘连蛋白不是单细胞行为和细胞形状变化所必需的。相反，在lama1(UW1)突变体中，上皮极性的丧失和改变的粘附导致有缺陷的组织结构和无序的视网膜的形成。这些结果表明，层粘连蛋白细胞外基质在调节粘附和极性以建立和维持视杯形态发生过程中的组织结构中起着多种关键作用。
