title: Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells.
abstract: Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissue-specific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.
authors.affiliation: Department of Anatomy, Department of Otorhinolaryngology, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea. bokj@yuhs.ac
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Bok
authors.forename: Colleen
authors.initials: C
authors.lastname: Zenczak
authors.forename: Chan Ho
authors.initials: CH
authors.lastname: Hwang
authors.forename: Doris K
authors.initials: DK
authors.lastname: Wu
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003857:Deoxyuridine / Q000031:analogs & derivatives; D006198:Hair Cells, Auditory / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009925:Organ of Corti / Q000166:cytology / Q000196:embryology*; D013136:Spiral Ganglion / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Atoh1; morphogenesis; tonotopy
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