RT Journal Article SR Electronic T1 Atoh1 Directs the Formation of Sensory Mosaics and Induces Cell Proliferation in the Postnatal Mammalian Cochlea In Vivo JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6699 OP 6710 DO 10.1523/JNEUROSCI.5420-11.2012 VO 32 IS 19 A1 Michael C. Kelly A1 Qing Chang A1 Alex Pan A1 Xi Lin A1 Ping Chen YR 2012 UL http://www.jneurosci.org/content/32/19/6699.abstract AB Hearing impairment due to the loss of sensory hair cells is permanent in humans. Considerable interest targets the hair cell differentiation factor Atoh1 as a potential tool with which to promote hair cell regeneration. We generated a novel mouse model to direct the expression of Atoh1 in a spatially and temporally specific manner in the postnatal mammalian cochlea to determine the competency of various types of cochlear epithelial cells for hair cell differentiation. Atoh1 can generate cells in young animals with morphological, molecular, and physiological properties reminiscent of hair cells. This competency is cell type specific and progressively restricted with age. Significantly, Atoh1 induces ectopic sensory patches through Notch signaling to form a cellular mosaic similar to the endogenous sensory epithelia and expansion of the sensory mosaic through the conversion of supporting cells and nonautonomous supporting cell production. Furthermore, Atoh1 also activates proliferation within the normally postmitotic cochlear epithelium. These results provide insight into the potential and limitations of Atoh1-mediated hair cell regeneration.