Brn-3b inhibits generation of amacrine cells by binding to and negatively regulating DLX1/2 in developing retina

L. Feng, D. D. Eisenstat, S. Chiba, Y. Ishizaki, L. Gan, K. Shibasaki

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

During retinogenesis, the basic helix-loop-helix proneural gene math5 (atoh7) initiates the generation of the first-born neurons, retinal ganglion cells (RGCs), by activating a network of RGC transcription factors, including Brn-3b (POU4F2). Herein, we show that the expression of DLX1 and DLX2 is significantly down-regulated in math5-null retina but is markedly increased in Brn-3b-null retina. Interestingly, Brn-3b interacts with DLX1 through its homeodomain, and this interaction represses DLX1 activity. Retrovirus-mediated mis-expression of DLX1 or DLX2 dramatically increases the number of amacrine/bipolar cells and concurrently reduces rod photoreceptors. Conversely, combined ectopic expression of Brn-3b with DLX1 or DLX2 promotes the production of RGCs and inhibits amacrine cell differentiation. Thus, DLX1/2 play an essential role in cell fate selection between amacrine and RGCs. Brn-3b suppresses the role of DLX1/2 through physical interaction and biases the competent precursors toward RGC fates.

Original languageEnglish (US)
Pages (from-to)9-20
Number of pages12
JournalNeuroscience
Volume195
DOIs
StatePublished - Nov 10 2011
Externally publishedYes

Keywords

  • Brn-3b
  • DLX1
  • DLX2
  • Development
  • Math5
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)

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