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First published online 23 April 2008
doi: 10.1242/dev.010751

Development 135, 1981-1990 (2008)
Published by The Company of Biologists 2008
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ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells

Ling Pan1, Min Deng1, Xiaoling Xie1 and Lin Gan1,2,3,*

1 Department of Ophthalmology, University of Rochester, Rochester, NY 14642, USA.
2 Center for Neural Development and Disease, University of Rochester, Rochester, NY 14642, USA.
3 Department of Neurobiology and Anatomy, University of Rochester, Rochester, NY 14642, USA.

* Author for correspondence (e-mail: lin_gan{at}urmc.rochester.edu)

Accepted 31 March 2008

LIM-homeodomain (HD) and POU-HD transcription factors play crucial roles in neurogenesis. However, it remains largely unknown how they cooperate in this process and what downstream target genes they regulate. Here, we show that ISL1, a LIM-HD protein, is co-expressed with BRN3B, a POU-HD factor, in nascent post-mitotic retinal ganglion cells (RGCs). Similar to the Brn3b-null retinas, retina-specific deletion of Isl1 results in the apoptosis of a majority of RGCs and in RGC axon guidance defects. The Isl1 and Brn3b double null mice display more severe retinal abnormalities with a near complete loss of RGCs, indicating the synergistic functions of these two factors. Furthermore, we show that both Isl1 and Brn3b function downstream of Math5 to regulate the expression of a common set of RGC-specific genes. Whole-retina chromatin immunoprecipitation and in vitro transactivation assays reveal that ISL1 and BRN3B concurrently bind to and synergistically regulate the expression of a common set of RGC-specific genes. Thus, our results uncover a novel regulatory mechanism of BRN3B and ISL1 in RGC differentiation.

Key words: LIM-homeodomain, POU domain, MATH5, ATOH7, POU4F2, RGC, Retinal development, Transcription factor






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