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First published online 8 November 2006
doi: 10.1242/dev.02664
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1 Center for Aging and Developmental Biology, University of Rochester,
Rochester, NY 14642, USA.
2 Department of Biology, University of Victoria, Victoria, BC V8W 3N5,
Canada.
3 Department of Ophthalmology, University of Rochester, Rochester, NY 14642,
USA.
4 Department of Neurobiology and Anatomy, University of Rochester, Rochester, NY
14642, USA.
* Author for correspondence (e-mail: lin_gan{at}urmc.rochester.edu)
Accepted 28 September 2006
The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes.
Key words: Bhlhb5 (Beta3), bHLH, Math5 (Atoh7), NeuroD (Neurod1), Math3 (Neurod4), Amacrine cell, Bipolar cell, Retina, Neurogenesis, Transcription factors, Mouse
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