Mechanisms of retinal photoreceptor development

光感受器是一种高度极化的神经元，也具有黏附连接等上皮性特征。为了研究光感受器细胞的极性形成机制，我们有条件地敲除了一个PKCλ，它被认为在利用Cre-loxP系统分化光感受器细胞的过程中起着关键的作用，在上皮和神经元的极性建立中起着关键作用。在λ条件性基因敲除小鼠中，光感受器细胞出现形态缺陷，不能形成带状突触。有趣的是，在分化光感受器时缺乏PKCλ，导致光感受器层乃至整个视网膜严重的板层结构紊乱。细胞命运的决定不受全层板层结构破坏的影响。胚胎12.5天发育中的光感受器开始表达Cre重组酶后，未成熟光感受器和有丝分裂前体细胞均散在分布于视网膜各部。我们检测到未成熟的光感受器和祖细胞之间的黏附连接形成在CKO视网膜中丢失，而在祖细胞之间保持。这些结果表明，在分化的光感受器中，蛋白激酶Cλ的表达是全视网膜分层所必需的。我们的数据表明，适当极化的光感受器将祖细胞锚定在神经视网膜的顶端边缘，这可能是建立正确的视网膜板层组织所必需的。

The photoreceptor is a highly polarized neuron and also has epithelial characteristics such as adherens junctions. To investigate the mechanisms of polarity formation of the photoreceptor cells, we conditionally knocked out aPKCλ, which has been proposed to play a critical role in the establishment of epithelial and neuronal polarity, in differentiating photoreceptor cells using the Cre-loxP system. In aPKCλ conditional knockout (CKO) mice, the photoreceptor cells displayed morphological defects and failed to form ribbon synapses. Intriguingly, lack of aPKCλ,in differentiating photoreceptors led to severe laminar disorganization not only in the photoreceptor layer but also in the entire retina. Cell fate detemination was not affected by total laminar disorganization. After Cre recombinase began to be expressed in the developing photoreceptors at embryonic day 12.5, both the immature photoreceptors and mitotic progenitors were dispersed throughout the CKO retina. We detected that adherens junction formation between the immature photoreceptors and the progenitors was lost in the CKO retina, while it was maintained between the progenitors themselves. These results indicate that the expression of aPKCλ in differentiating photoreceptors is required for total retinal lamination. Our data suggest that properly polarized photoreceptors anchor progenitors at the apical edge of the neural retina, which may be essential for building correct laminar organization of the retina.