LMO4 functions as a co-activator of neurogenin 2 in the developing cortex. Academic Article uri icon

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.

published proceedings

  • Development

altmetric score

  • 1

author list (cited authors)

  • Asprer, J., Lee, B., Wu, C., Vadakkan, T., Dickinson, M. E., Lu, H., & Lee, S.

citation count

  • 28

complete list of authors

  • Asprer, Joanna ST||Lee, Bora||Wu, Chia-Shan||Vadakkan, Tegy||Dickinson, Mary E||Lu, Hui-Chen||Lee, Soo-Kyung

publication date

  • July 2011