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Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

Authors
 Jinwoong Bok  ;  Colleen Zenczak  ;  Chan Ho Hwang  ;  Doris K. Wu 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.110(34) : 13869-13874, 2013 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2013
MeSH
Animals ; Cell Cycle Checkpoints/physiology* ; Cell Differentiation/physiology* ; Deoxyuridine/analogs & derivatives ; Hair Cells, Auditory/physiology* ; Hedgehog Proteins/metabolism* ; In Situ Hybridization ; In Situ Nick-End Labeling ; Mice ; Morphogenesis/physiology* ; Organ of Corti/cytology ; Organ of Corti/embryology* ; Spiral Ganglion/metabolism*
Keywords
Atoh1 ; morphogenesis ; tonotopy
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.
Files in This Item:
T201302795.pdf Download
DOI
10.1073/pnas.1222341110
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87619
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