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W. Ma, S.–Z. Wang; Evidence for two pathways leading to neuroD expression and photoreceptor genesis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5319.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The developing vertebrate retina expresses several bHLH genes homologous to the Drosophila proneural genes. How these genes network leading to the generation of the various types of retinal cells is poorly understood. Previous studies indicate that neuroD is likely a pro–photoreceptor gene, and neurogenin2 (ngn2) functions in retinal progenitor cells and may lead progenitor cells to various pathways, including the photoreceptor pathway and the ganglion cell pathway. Ath5, another bHLH gene, has been shown to play an important role in retinal ganglion cell development. This study examines the genetic relationship among ngn2, neuroD, and cath5. Methods: . RCAS, a replication–competent retrovirus, was used to drive ectopic expression of bHLH genes in cultured RPE cells derived from day 6 chick embryos. Cells were then either fixed for immunocytochemistry or harvested for RT–PCR analyses of the induction of gene expression. Results: Ectopic expression of cath5 in cultured RPE cells induced the expression of visinin, a gene encoding calcium–binding protein in chick photoreceptor cells. The Visinin+ cells closely resembled developing photoreceptor cells in a retinal cell culture. On polyornithine–coated coverslips, Visinin+ cells developed typical photoreceptor morphologies, such as an elongated cell body, an axon often with elaborate arboration, and inner segment–like and even outer segment–like structures. The manifestation of the morphological differentiation suggests that cath5 trigged RPE transdifferentiation towards photoreceptor cells and induced a spectrum of genes associated with photoreceptor development and differentiation. Morphologically, the Visinin+ cells generated from ectopic cath5 expression appeared comparable with those generated with ectopic neuroD or ngn2. Nonetheless, the number of Visinin+ cells was lower with cath5 than with neuroD or ngn2. Like ngn2, cath5 induced neuroD expression, but not vise versa. Neither ngn2 induced cath5 nor cath5 induced ngn2. Thus, ngn2 and cath5 might represent different photoreceptor pathways that merged at neuroD expression. Conclusions: Our data suggest (i) cath5 may lead to photoreceptor genesis and this is likely to be mediated through neuroD; and (ii) the pathway of cath5 → neuroD → photoreceptor genes converges with that of ngn2 → neuroD → photoreceptor genes. Thus, there may exist two separate pathways leading to neuroD expression and photoreceptor genesis.
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