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


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.

SUBMITTER: Asprer JS 

PROVIDER: S-EPMC3109604 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Asprer Joanna S T JS   Lee Bora B   Wu Chia-Shan CS   Vadakkan Tegy T   Dickinson Mary E ME   Lu Hui-Chen HC   Lee Soo-Kyung SK  

Development (Cambridge, England) 20110701 13


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 transcri  ...[more]

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