LMO4 functions as a co-activator of neurogenin 2 in the developing cortex

Joanna S.T. Asprer, Bora Lee, Chia Shan Wu, Tegy Vadakkan, Mary E. Dickinson, Hui Chen Lu, Soo Kyung Lee

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The proneural protein neurogenin 2 (NGN2) is a key transcription factor in regulating both neurogenesis and neuronal radial migration in the embryonic cerebral cortex. However, the co-factors that support the action of NGN2 in the cortex remain unclear. Here, we show that the LIM-only protein LMO4 functions as a novel co-factor of NGN2 in the developing cortex. LMO4 and its binding partner nuclear LIM interactor (NLI/LDB1/CLIM2) interact with NGN2 simultaneously, forming a multi-protein transcription complex. This complex is recruited to the E-box containing enhancers of NGN2-target genes, which regulate various aspects of cortical development, and activates NGN2-mediated transcription. Correspondingly, analysis of Lmo4-null embryos shows that the loss of LMO4 leads to impairments of neuronal differentiation in the cortex. In addition, expression of LMO4 facilitates NGN2-mediated radial migration of cortical neurons in the embryonic cortex. Our results indicate that LMO4 promotes the acquisition of cortical neuronal identities by forming a complex with NGN2 and subsequently activating NGN2-dependent gene expression.

Original languageEnglish (US)
Pages (from-to)2823-2832
Number of pages10
JournalDevelopment
Volume138
Issue number13
DOIs
StatePublished - Jul 1 2011

Keywords

  • Basic helix-loop-helix factor
  • Cortex development
  • LIM domain
  • LMO4
  • Mouse
  • NGN2
  • NLI

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Asprer, J. S. T., Lee, B., Wu, C. S., Vadakkan, T., Dickinson, M. E., Lu, H. C., & Lee, S. K. (2011). LMO4 functions as a co-activator of neurogenin 2 in the developing cortex. Development, 138(13), 2823-2832. https://doi.org/10.1242/dev.061879