Activation of the bHLH factor Math5 (Atoh7) is an initiating event for mammalian retinal neurogenesis, as it is critically required for retinal ganglion cell formation. However, the cis-regulatory elements and trans-acting factors that control Math5 expression are largely unknown. Using a combination of transgenic mice and bioinformatics, we identified a phylogenetically conserved regulatory element that is required to activate Math5 transcription during early retinal neurogenesis. This element drives retinal expression in vivo, in a cross-species transgenic assay. Previously, Pax6 was shown to be necessary for the initiation of Math5 mRNA expression. We extend this finding by showing that the Math5 retinal enhancer also requires Pax6 for its activation, via Pax6 binding to a highly conserved binding site. In addition, our data reveal that other retinal factors are required for accurate regulation of Math5 by Pax6.
PubMed ID: 19208436
PMC ID: PMC2976517
Article link: Genesis.
Grant support: EY12274 NEI NIH HHS , EY13612 NEI NIH HHS , R01 EY012274-10 NEI NIH HHS , R01 EY013612-09A1 NEI NIH HHS , R01 EY012274-14 NEI NIH HHS , R01 EY012274 NEI NIH HHS , R01 EY013612 NEI NIH HHS , EY12274 NEI NIH HHS , R01 EY013612 NEI NIH HHS , R01 EY013612-09A1 NEI NIH HHS , EY13612 NEI NIH HHS , R01 EY012274 NEI NIH HHS , R01 EY012274-10 NEI NIH HHS
Genes referenced: atoh7 pax6