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First published online 18 February 2004
doi: 10.1242/dev.01010
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1 Department of Biochemistry and Molecular Biology, The University of Texas M.
D. Anderson Cancer Center, Houston, TX 77030, USA
2 Department of Biology and The Laboratory for Functional Genomics, Texas
A&M University, College Station, TX 77843-3285, USA
3 Department of Biomathematics, The University of Texas M. D. Anderson Cancer
Center, Houston, TX 77030, USA
4 Department of Molecular Genetics, The University of Texas M. D. Anderson
Cancer Center, Houston, TX 77030, USA
* Author for correspondence (e-mail: wklein{at}mdanderson.org)
Accepted 27 November 2003
Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that is essential for retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. Our goal was to establish a link between Brn3b and the downstream events leading to RGC differentiation. We sought to determine both the number and types of genes that depend on Brn3b for their expression. RNA probes from wild-type and Brn3b-/- E14.5, E16.5 and E18.5 mouse retinas were hybridized to a microarray containing 18,816 retina-expressed cDNAs. At E14.5, we identified 87 genes whose expression was significantly altered in the absence of Brn3b and verified the results by real-time PCR and in situ hybridization. These genes fell into discrete sets that encoded transcription factors, proteins associated with neuron integrity and function, and secreted signaling molecules. We found that Brn3b influenced gene expression in non RGCs of the retina by controlling the expression of secreted signaling molecules such as sonic hedgehog and myostatin/Gdf8. At later developmental stages, additional alterations in gene expression were secondary consequences of aberrant RGC differentiation caused by the absence of Brn3b. Our results demonstrate that a small but crucial fraction of the RGC transcriptome is dependent on Brn3b. The Brn3b-dependent gene sets therefore provide a unique molecular signature for the developing retina.
Key words: POU domain transcription factor, Brn3b/Brn-3.2/POU4f2, Mouse embryonic retina, Microarray gene expression profiling
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