The crumbs (crb) apical polarity genes are essential for the development and functions of epithelia. Adult zebrafish retinal neuroepithelium expresses three crb genes (crb1, crb2a, and crb2b); however, it is unknown whether and how Crb1 differs from other Crb proteins in expression, localization, and functions. Here, we show that, unlike zebrafish Crb2a and Crb2b as well as mammalian Crb1 and Crb2, zebrafish Crb1 does not localize to the subapical regions of photoreceptors and Müller glial cells; rather, it localizes to a small region of cone outer segments: the cell membranes surrounding the axonemes. Moreover, zebrafish Crb1 is not required for retinal morphogenesis and photoreceptor patterning. Interestingly, Crb1 promotes rod survival under strong white light irradiation in a previously unreported non--cell-autonomous fashion; in addition, Crb1 delays UV and blue cones' chromatin condensation caused by UV light irradiation. Finally, Crb1 plays a role in cones' responsiveness to light through an arrestin-translocation-independent mechanism. The localization of Crb1 and its functions do not differ between male and female fish. We conclude that zebrafish Crb1 has diverged from other vertebrate Crb proteins, representing a neofunctionalization in Crb biology during evolution.

SIGNIFICANCE STATEMENT Apicobasal polarity of epithelia is an important property that underlies the morphogenesis and functions of epithelial tissues. Epithelial apicobasal polarity is controlled by many polarity genes, including the crb genes. In vertebrates, multiple crb genes have been identified, but the differences in their expression patterns and functions are not fully understood. Here, we report a novel subcellular localization of zebrafish Crb1 in retinal cone photoreceptors and evidence for its new functions in photoreceptor maintenance and light responsiveness. This study expands our understanding of the biology of the crb genes in epithelia, including retinal neuroepithelium.

该屑（CRB）心尖极性基因是上皮细胞的发育和功能是必不可少的。成年斑马鱼视网膜神经上皮细胞表达三个crb基因（crb1，crb2a和crb2b）; 但是，尚不清楚Crb1在表达，定位和功能上是否与其他Crb蛋白不同，以及如何与其他Crb蛋白不同。在这里，我们表明，与斑马鱼Crb2a和Crb2b以及哺乳动物Crb1和Crb2不同，斑马鱼Crb1并不位于感光器和Müller神经胶质细胞的根尖区域。相反，它定位在锥体外部部分的一小部分：围绕着轴突的细胞膜。此外，斑马鱼Crb1不需要为视网膜形态发生和感光器模式。有趣的是，Crb1以以前从未报道的非细胞自主方式促进强白光照射下棒的存活。另外，Crb1延迟了紫外线和蓝锥因紫外线照射引起的染色质凝结。最后，Crb1在视锥细胞的 通过抑制素转运独立机制对光的反应性。雄性和雌性鱼类中Crb1的定位及其功能没有差异。我们得出的结论是，斑马鱼Crb1与其他脊椎动物Crb蛋白不同，代表了进化过程中Crb生物学的新功能。

意义声明上皮的顶基极性是重要的特性，是上皮组织的形态发生和功能的基础。上皮末梢突触极性受许多极性基因控制，包括crb基因。在脊椎动物中，已经鉴定了多个crb基因，但是它们的表达方式和功能的差异尚不完全清楚。在这里，我们报告斑马鱼Crb1在视网膜锥感光细胞中的新型亚细胞定位及其在感光细胞维持和光反应性中的新功能的证据。这项研究扩大了我们对包括视网膜神经上皮在内的上皮细胞中crb基因生物学的理解。