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Mechanisms of retinal photoreceptor development

视网膜感光器发育机制

基本信息

批准号：
16300115
负责人：
FURUKAWA Takahisa
金额：
$ 8.32万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300115/
关键词：
retina photoreceptor cell cell polarity adherence function laver formation pineal gland synapse formation transcription factor otx2 mr-s FGF receptor プロモーター

项目摘要

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.

光感受器是一种高度极化的神经元，也具有上皮特征，如粘附连接。为了研究感光细胞极性形成的机制，我们使用Cre-loxP系统在感光细胞分化中条件性地敲除aPKC λ，该aPKC λ被认为在上皮和神经元极性的建立中起关键作用。在aPKC λ条件性敲除（CKO）小鼠中，感光细胞显示形态缺陷，并且不能形成带状突触。有趣的是，在分化光感受器中缺乏aPKC λ，不仅在光感受器层而且在整个视网膜中导致严重的层状结构紊乱。细胞命运的测定不受全层结构紊乱的影响。Cre重组酶在胚胎第12.5天开始在发育中的光感受器中表达后，未成熟的光感受器和有丝分裂的祖细胞都分散在CKO视网膜中。我们检测到未成熟的光感受器和祖细胞之间的粘附连接形成在CKO视网膜中丢失，而它在祖细胞本身之间维持。这些结果表明，aPKC λ在分化的光感受器中的表达是整个视网膜分层所必需的。我们的数据表明，正确极化的光感受器锚祖细胞在神经视网膜的顶端边缘，这可能是必不可少的建立正确的层状组织的视网膜。