spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

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

Development 135, 1981-1990 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
dev.010751v1
135/11/1981    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Pan, L.
Right arrow Articles by Gan, L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pan, L.
Right arrow Articles by Gan, L.

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






© The Company of Biologists Ltd 2008