LMO4 functions as a co-activator of neurogenin 2 in the developing cortex
LMO4 functions as a co-activator of neurogenin 2 in the developing cortex
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.
- Baylor College of Medicine United States
- OREGON HEALTH & SCIENCE UNIVERSITY
- Vollum Institute United States
- Oregon Health & Science University United States
- BAYLOR COLLEGE OF MEDICINE
Cerebral Cortex, Homeodomain Proteins, Chromatin Immunoprecipitation, Reverse Transcriptase Polymerase Chain Reaction, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Cell Differentiation, Nerve Tissue Proteins, LIM Domain Proteins, DNA-Binding Proteins, Mice, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, Animals, In Situ Hybridization, Adaptor Proteins, Signal Transducing, Protein Binding, Transcription Factors
Cerebral Cortex, Homeodomain Proteins, Chromatin Immunoprecipitation, Reverse Transcriptase Polymerase Chain Reaction, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Cell Differentiation, Nerve Tissue Proteins, LIM Domain Proteins, DNA-Binding Proteins, Mice, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, Animals, In Situ Hybridization, Adaptor Proteins, Signal Transducing, Protein Binding, Transcription Factors
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