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W. Ma, R.-T. Yan, W. Mao, S.-Z. Wang; Neurogenin-Related 3 Controls Regulatory Genes in Retinal Neurogenesis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3214.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the cross-regulation of bHLH factors that constitutes an essential element in the transcriptional regulatory network governing retinal neurogenesis.
A chick bHLH gene homologous to the mammalian neurogenin 3, hence named neurogenin-related 3 (ngnr-3), was isolated. The role of ngnr-3 in regulating retina neurogenesis was studied through gain-of-function using RCAS retroviral transduction.
In the retina, ngnr-3 expression was temporally confined to early neurogenesis and spatially restricted to the anatomical location of M-phase cells. Retroviral-driven overexpression of ngnr-3 in the developing chick retina altered the expression of regulatory genes associated with different cell populations. Ash1 and ngn2 were repressed. Expression of neuroD, ngn1, and sox2 was spatially extended and/or temporally prolonged. The spatial locales of ath3 and chx10 expression were altered. The expression of ath5 in the ganglion cell region was enhanced and in the progenitor cell region diminished. Furthermore, ngnr-3 overexpression promoted cell cycle withdrawal, expanded the expression of ganglion cell markers, and reduced the expression of amacrine cell markers. When ectopically expressed in cultured, non-neural RPE cells, ngnr-3 induced genes normally expressed in retinal progenitor cells and elicited, de novo, cells that resembled retinal neurons molecularly, morphologically, and physiologically.
These results suggest an intricate, regulatory role of ngnr-3 in initiating retinal neurogenesis by promoting cell cycle exit, inducing regulatory genes for early-born neurons, and repressing those for later-born cells.
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