Abstract
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 IsI1 results in the apoptosis of a majority of RGCs and in RGC axon guidance defects. The IsI1 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 IsI1 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.
Original language | English (US) |
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Pages (from-to) | 1981-1990 |
Number of pages | 10 |
Journal | Development |
Volume | 135 |
Issue number | 11 |
DOIs | |
State | Published - Jun 2008 |
Externally published | Yes |
Keywords
- ATOH7
- LIM-homeodomain
- MATHS
- POU domain
- POU4F2
- RGC
- Retinal development
- Transcription factor
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology