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W. Mao, R.–T. Yan, W. Ma, S.–Z. Wang; Proneural bHLH Gene Ash1 Promotes Amacrine Cell Production . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3128.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To gain insight into the genetic regulation of retinal cell fate specification, we began to investigate the role of proneural bHLH gene ash1 in retinal neurogenesis. Methods: Replication–competent retrovirus RCAS was used to drive ash1 misexpression in the developing chick retina or ash1 ectopic expression in cultured RPE cells. We used molecular and morphological criteria to analyze the effects of these manipulations on retinal development and on RPE transdifferentiation along retinal neural pathways. Results: RCAS–driven misexpression of ash1 in chick embryos resulted in conspicuous eye phenotypes, including microphthalmia and corneal extrusion. Since ash1 is abundantly expressed in the retina, we reasoned that ash1 might play a critical role in retinal development. Indeed, in retinas infected with RCAS–ash1 we observed that the number of amacrine cells was increased, while the numbers of other inner neurons, such as bipolar cells and horizontal cells, were not. Notably, photoreceptor cells were profoundly diminished upon ash1 misexpression. When ectopically expressed in cultured RPE cells, ash1 elicited RPE transdifferentiation into cells that morphologically resembled neurons with long, thin, and branching processes. These cells expressed neural makers that are expressed in amacrine cells. However, the cultures had no significant number of cells positive for Visinin, a photoreceptor marker. RT–PCR showed a lack of induction of visinin and neuroD. Conclusions: Our study indicates that ash1 may regulate genes critical to normal eye development. In the retina, ash1 promotes amacrine cell production and possibly biases against photoreceptor cells.
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