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The Journal of Neuroscience, November 2, 2005, 25(44):10290-10298; doi:10.1523/JNEUROSCI.3657-05.2005

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Development/Plasticity/Repair
Function of Atypical Protein Kinase C {lambda} in Differentiating Photoreceptors Is Required for Proper Lamination of Mouse Retina

Chieko Koike,1 Akihiro Nishida,1 Kazunori Akimoto,3 Masa-aki Nakaya,3 Tetsuo Noda,4 Shigeo Ohno,3 and Takahisa Furukawa1,2

1Department of Developmental Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan, 2Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan, 3Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 239-0004, Japan, and 4Department of Cell Biology, Cancer Institute, Tokyo 135-8550, Japan

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 atypical protein kinase C{lambda} (aPKC{lambda}), 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 aPKC{lambda} conditional knock-out (CKO) mice, the photoreceptor cells displayed morphological defects and failed to form ribbon synapses. Intriguingly, lack of aPKC{lambda} in differentiating photoreceptors led to severe laminar disorganization not only in the photoreceptor layer but also in the entire retina. Cell fate determination 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, whereas it was maintained between the progenitors themselves. These results indicate that the expression of aPKC{lambda} 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.

Key words: aPKC; retina; photoreceptor; lamina; polarity; adherens junction; cadherin; catenin


Received April 27, 2005; revised September 26, 2005; accepted September 28, 2005.




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