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.

光感受器是高度极化的神经元，也具有上皮特征，例如粘附连接。为了研究光感受器细胞的极性形成的机制，我们有条件地淘汰了APKCλ，该APKCλ在使用CRE-LOXP系统区分受感受器细胞中，在上皮和神经元极性的建立中起着至关重要的作用。在APKCλ条件敲除（CKO）小鼠中，光感受器细胞表现出形态缺陷，未能形成色带突触。有趣的是，缺乏APKCλ，在区分光感受器中，不仅在光感受器层中而且在整个视网膜中也导致严重的层流杂交。细胞致命的局势不受总层流杂交的影响。在CRE重组酶在胚胎第12.5天发育的感光体中开始表达后，未成熟的感光体和有丝分裂祖细胞均分散在整个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，而祖细胞本身之间则保持了连接。这些结果表明，总视网膜层压层需要APKCλ在分化感光体中的表达。我们的数据表明，在神经视网膜的顶端边缘上适当极化的光感受器锚定祖细胞，这对于构建视网膜的正确层流组织至关重要。