Intact Retinal Pigment Epithelium Maintained by Nok Is Essential for Retinal Epithelial Polarity and Cellular Patterning in Zebrafish

Within the vertebrate eye, the retinal pigment epithelium (RPE) juxtaposes with the retina, but how the RPE plays a role in retinal morphogenesis remains elusive. It has been shown that the loss of function of the polarity proteins, such as Nagie oko (Nok), disrupts RPE integrity and retinal lamination. However, it is unclear whether or not such defects are caused in a tissue-autonomous manner. Here, by taking advantage of the nok mutation, we have generated a transgenic model to restore the Nok function in the RPE, but not in the retina. With this model, we show that Nok is required for RPE integrity in a tissue-autonomous manner. However, proper retinal epithelial polarity does not require retinal expression of Nok before embryonic photoreceptor genesis; rather, it requires a Nok-mediated intact RPE. Interestingly, sporadic wild-type RPE donor cells are not sufficient to maintain proper retinal polarity. We further show that RPE-mediated retinal epithelial polarity underlies proper patterning of retinal ganglion cells and the cells of the inner nuclear layer. Nevertheless, during embryonic photoreceptor genesis, an intact RPE is not sufficient to maintain retinal epithelial polarity and retinal cellular pattern formation. Our results show that the subcellular architecture and cellular pattern formation of a tissue may be regulated by neighboring tissues through tissue-tissue interactions.