title: Lhx6 and Lhx8 coordinately induce neuronal expression of Shh that controls the generation of interneuron progenitors.
abstract: Lhx6 and Lhx8 transcription factor coexpression in early-born MGE neurons is required to induce neuronal Shh expression. We provide evidence that these transcription factors regulate expression of a Shh enhancer in MGE neurons. Lhx6 and Lhx8 are also required to prevent Nkx2-1 expression in a subset of pallial interneurons. Shh function in early-born MGE neurons was determined by genetically eliminating Shh expression in the MGE mantle zone (MZ). This mutant had reduced SHH signaling in the overlying progenitor zone, which led to reduced Lhx6, Lhx8, and Nkx2-1 expression in the rostrodorsal MGE and a preferential reduction of late-born somatostatin(+) and parvalbumin(+) cortical interneurons. Thus, Lhx6 and Lhx8 regulate MGE development through autonomous and nonautonomous mechanisms, the latter by promoting Shh expression in MGE neurons, which in turn feeds forward to promote the developmental program of the rostrodorsal MGE.
authors.affiliation: Department of Psychiatry and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Flandin
authors.forename: Yangu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Daniel
authors.initials: D
authors.lastname: Vogt
authors.forename: Juhee
authors.initials: J
authors.lastname: Jeong
authors.forename: Jason
authors.initials: J
authors.lastname: Long
authors.forename: Gregory
authors.initials: G
authors.lastname: Potter
authors.forename: Heiner
authors.initials: H
authors.lastname: Westphal
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005829:Geniculate Bodies / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C498504:LHX6 protein, mouse; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; C465570:Shh protein, mouse; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors