title: 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.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joanna S T
authors.initials: JS
authors.lastname: Asprer
authors.forename: Bora
authors.initials: B
authors.lastname: Lee
authors.forename: Chia-Shan
authors.initials: CS
authors.lastname: Wu
authors.forename: Tegy
authors.initials: T
authors.lastname: Vadakkan
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C102084:Ldb1 protein, mouse; C491976:Lmo4 protein, mouse; C102938:Neurog2 protein, mouse