Abstract

Light is translated into neural signals by neuroepithelial cells in the retina. Development of neural and glial cell classes within the retina occurs in an overlapping, highly organized fashion. Retinal ganglion cells form first, followed by cone photoreceptors, amacrine, horizontal interneurons, rod photoreceptors, and finally bipolar interneurons and Müller glia. Clonal analyses revealed that these cell classes differentiate from a common pool of multipotent progenitor cells, whose developmental potential shifts across embryonic and early postnatal life. Retinal progenitor cell competence is regulated by both intrinsic and extrinsic factors. Intrinsic factors, which include those with homeobox and basic helix-loop-helix protein motifs, regulate early eye growth patterning and retinal cell type specification. Moreover, miRNAs and epigenetic regulators constitute an additional layer of transcriptional regulation of retinal development. Extrinsic factors are also important for optic cup growth and regulate the proportions of each retinal cell class present in the mature retina. Finally, mutations in intrinsic or extrinsic factors are important causes of human congenital or degenerative retinal diseases. The actions of these molecules are the focus of intense research to develop retinal gene and stem cell therapies.

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