Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Eye Proteins / biosynthesis*
-
Eye Proteins / genetics
-
Gene Expression Regulation, Developmental / physiology*
-
Homeodomain Proteins / biosynthesis*
-
Homeodomain Proteins / genetics
-
Mice
-
Mice, Mutant Strains
-
Mice, Transgenic
-
Nerve Tissue Proteins / biosynthesis*
-
Nerve Tissue Proteins / genetics
-
Neurogenesis / physiology*
-
PAX6 Transcription Factor
-
Paired Box Transcription Factors / biosynthesis*
-
Paired Box Transcription Factors / genetics
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
Repressor Proteins / biosynthesis*
-
Repressor Proteins / genetics
-
Response Elements / physiology*
-
Retinal Ganglion Cells / cytology
-
Retinal Ganglion Cells / metabolism*
-
Transcription, Genetic / physiology
-
Xenopus
Substances
-
Atoh7 protein, mouse
-
Basic Helix-Loop-Helix Transcription Factors
-
Eye Proteins
-
Homeodomain Proteins
-
Nerve Tissue Proteins
-
PAX6 Transcription Factor
-
Paired Box Transcription Factors
-
Pax6 protein, mouse
-
RNA, Messenger
-
Repressor Proteins