Commissural neuron identity is specified by a homeodomain protein, Mbh1, that is directly downstream of Math1.
Proneural basic helix-loop-helix (bHLH) proteins are key regulators of neurogenesis. However, downstream target genes of the bHLH proteins remain poorly defined. Mbh1 confers commissural neuron identity in the spinal cord. Enhancer analysis using transgenic mice revealed that Mbh1 expression required an E-box 3' of the Mbh1 gene. Mbh1 expression was lost in Math1 knockout mice, whereas misexpression of Math1 induced ectopic expression of Mbh1. Moreover, Math1 bound the Mbh1 enhancer containing the E-box in vivo and activated gene expression. Generation of commissural neurons by Math1 was inhibited by a dominant negative form of Mbh1. These findings indicate that Mbh1 is necessary and sufficient for the specification of commissural neurons, as a direct downstream target of Math1.
Saba
Rie
R
Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Johnson
Jane E
JE
Saito
Tetsuichiro
T
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024721:E-Box Elements; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C500942:ATOH1 protein, human; C500943:Atoh1 protein, mouse; C483826:Capg protein, mouse