ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells

Ling Pan, Min Deng, Xiaoling Xie, Lin Gan

Research output: Contribution to journalArticle

117 Scopus citations

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 languageEnglish (US)
Pages (from-to)1981-1990
Number of pages10
JournalDevelopment
Volume135
Issue number11
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Keywords

  • ATOH7
  • LIM-homeodomain
  • MATHS
  • POU domain
  • POU4F2
  • Retinal development
  • RGC
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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