Jinwoong Boka,1,2, Colleen Zenczakb,1, Chan Ho Hwangb,3, and Doris K. Wub,2
aDepartment of Anatomy, Department of Otorhinolaryngology, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Korea and
bLaboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850
Edited by Huda Y. Zoghbi, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, and approved July 12, 2013 (received for review December 28, 2012)
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.
morphogenesis, Atoh1, tonotopy
1J.B. and C.Z. contributed equally to this work.
2To whom correspondence may be addressed.
3Present address: Yangcheon Seoul ENT Clinic, 49 Mokdong-seoro, Yangcheon-gu, Seoul 158-878, South Korea.
Author contributions: J.B., C.Z., C.H.H., and D.K.W. designed research; J.B., C.Z., and C.H.H. performed research; J.B., C.Z., C.H.H., and D.K.W. analyzed data; and J.B., C.Z., and D.K.W. wrote the paper.