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PMID:18434421
| Citation |
Pan, L, Deng, M, Xie, X and Gan, L (2008) ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells. Development 135:1981-90 |
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| 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 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. |
| Links |
PubMed PMC2758274 Online version:10.1242/dev.010751 |
| Keywords |
Animals; Cell Differentiation/genetics; Cell Differentiation/physiology; Chromatin Immunoprecipitation; Gene Expression Regulation, Developmental; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Homeodomain Proteins/physiology; Immunohistochemistry; In Situ Hybridization; LIM-Homeodomain Proteins; Mice; Mice, Knockout; Mitosis; Promoter Regions, Genetic/genetics; Protein Binding; Retina/cytology; Retina/embryology; Retina/metabolism; Retinal Ganglion Cells/cytology; Retinal Ganglion Cells/metabolism; Transcription Factor Brn-3B/genetics; Transcription Factor Brn-3B/metabolism; Transcription Factor Brn-3B/physiology; Transcription Factors |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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