title: Patterning of ventral telencephalon requires positive function of Gli transcription factors.
abstract: The ability of neuroepithelial cells to generate a diverse array of neurons is influenced by locally secreted signals. In the spinal cord, Sonic Hedgehog (Shh) is known to induce distinct cell fates in a concentration-dependent manner by regulating the activities of the three Gli transcription factors in neural precursors. However, whether Gli-mediated Shh signaling is also required to induce different cell types in the ventral telencephalon has been controversial. In particular, loss of Shh has little effect on dorsoventral patterning of the telencephalon when Gli3 is also removed. Furthermore, no ventral telencephalic phenotypes have been found in individual Gli mutants. To address this issue, we first characterized Shh-responding ventral telencephalic progenitors between E9.5 and E12.5 and found that they produce neurons migrating to different layers of the cortex. We also discovered a loss of Nkx2.1 and Nkx6.2 expression in two subgroups of progenitors in embryos lacking major Gli activators. Finally, we analyzed the telencephalic phenotypes of embryos lacking all Gli genes and found that the ventral telencephalon was highly disorganized with intermingling of distinct neuronal cell types. Together, these studies unravel a role for Gli transcription factors in mediating Shh signaling to control specification, differentiation and positioning of ventral telencephalic neurons.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Weiying
authors.initials: W
authors.lastname: Yu
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Kristen
authors.initials: K
authors.lastname: McDonnell
authors.forename: Daniel
authors.initials: D
authors.lastname: Stephen
authors.forename: C Brian
authors.initials: CB
authors.lastname: Bai
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D013687:Telencephalon / Q000196:embryology / Q000254:growth & development*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C000614414:Nkx2-1 protein, mouse; C117745:Nkx6-2 protein, mouse; D009687:Nuclear Proteins; C465570:Shh protein, mouse; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3