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Am J Physiol Cell Physiol 296: C441-C452, 2009. First published December 17, 2008; doi:10.1152/ajpcell.00324.2008
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NERVOUS SYSTEM CELL BIOLOGY

Directed differentiation of mouse cochlear neural progenitors in vitro

Jizhen Lin,1,4,* Ling Feng,1,* Yuki Hamajima,1 Masahiro Komori,1 Terry C. Burns,2,3,4 Shinji Fukudome,1 John Anderson,1,2 Dong Wang,5 Catherine M. Verfaillie,4 and Walter C. Low2,3,4

Departments of 1Otolaryngology and 2Neurosurgery, 3Graduate Program in Neuroscience, 4Stem Cell Institute, and 5Bioengineering, University of Minnesota, Minneapolis, Minnesota

Submitted 18 June 2008 ; accepted in final form 7 December 2008

Multipotent cochlear neural progenitors (CNPs) in the organ of Corti hold the promise for cell replacement in degenerative hearing disorders. However, not much is known about the CNPs and the specific conditions for their differentiation. Here we isolate the CNPs from the postnatal day 1 organ of Corti in mice and demonstrate their capability to self-renew and to differentiate into hair cell-like and neuronal cell-like phenotypes under the guidance of sonic hedgehog (SHH), epidermal growth factor (EGF), retinoic acid (RA), and brain-derived neurotrophic factor (BDNF), herein termed SERB (abbreviation of SHH, EGF, RA, and BDNF) in an asymmetric or symmetric manner from clonal isolates. Differentiation of CNPs into hair cells by SERB was dependent on the ERK signaling pathway, whereas the differentiation of CNPs into neurons by SERB was not. This work develops a new in vitro methodology for the maintenance and self-regeneration of CNPs for future design of regenerative strategies for hearing disorders.

growth factor; proliferation



Address for reprint requests and other correspondence: J. Lin, 216 Lions Research Bldg., Univ. of Minnesota, 2001 Sixth St. S.E., Minneapolis, MN 55455 (e-mail: linxx004{at}tc.umn.edu)







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