title: Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord.
abstract: The molecular programs that specify progenitors in the dorsal spinal cord remain poorly defined. The homeodomain transcription factor Gsh2 is expressed in the progenitors of three dorsal interneuron subtypes, dI3, dI4 and dI5 neurons, whereas Gsh1 is only expressed in dI4 and dI5 progenitors. Mice lacking Gsh2 exhibit a selective loss of dI3 interneurons that is accompanied by an expansion of the dI2 progenitor domain. In Gsh2 mutant embryos, expression of the proneural bHLH protein Mash1 is downregulated in dI3 neural progenitors, with Mash1 mutants exhibiting a concordant reduction in dI3 neurons. Conversely, overexpression of Gsh2 and Mash1 leads to the ectopic production of dI3 neurons and a concomitant repression of Ngn1 expression. Our results provide evidence that genetic interactions involving repression of Ngn1 by Gsh2 promote the differentiation of dI3 neurons from class A progenitors.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. goulding@salk.edu
authors.forename: Sonja
authors.initials: S
authors.lastname: Kriks
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Lanuza
authors.forename: Rumiko
authors.initials: R
authors.lastname: Mizuguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Nakafuku
authors.forename: Martyn
authors.initials: M
authors.lastname: Goulding
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D013116:Spinal Cord / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C098513:Gsh1 protein, mouse; C109498:Gsh2 protein, mouse; C486336:Neurog1 protein, mouse