title: Smoothened controls cyclin D2 expression and regulates the generation of intermediate progenitors in the developing cortex.
abstract: Translocation of the Smoothened to the cell membrane is critical for sonic hedgehog activity. However, the biological importance of Smoothened itself has not been fully studied. To address this issue, we disabled Smoothened specifically in the dorsal telencephalon. Birth-date analysis and layer marker expression patterns revealed the slightly impaired development of the superficial layer neurons in the embryos of Emx1-Cre; Smoothened(fl/-) conditional knockout mice. Further analysis of the mutant embryos revealed a decrease in the number of intermediate progenitor cells. In the knockout mice, the expression of cyclin D2, but not cyclin D1 or cyclin E, was reduced in the dorsal telencephalon. In addition, the projections of dopaminergic neurons were affected during development, and the number of activated astrocytes was increased in the neocortex of the mutant mice. Our data suggest that Smoothened signaling, acting through cyclin D2, is critical for the proper development and maturation of the neocortex.
authors.affiliation: Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, 23 Matsuokashimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Komada
authors.forename: Tokuichi
authors.initials: T
authors.lastname: Iguchi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Takeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D056742:Cyclin D2 / Q000378:metabolism*; D004622:Embryo, Mammalian; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000196:embryology*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000072086:Smoothened Receptor
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor