Submitted on June 18, 2008
Revised on December 1, 2008
Accepted on December 7, 2008
Directed Differentiation of Mouse Cochlear Neural Progenitors in vitro
Jizhen n/a Lin1*, Ling Feng1, Yuki Hamajima2, Masahiro Komori3, Terry C Burns1, Shinji Fukodome4, John Anderson1, Dong Wang1, Catherine M Verfaillie1, and Walter Low1
1 University of Minnesota
2 Nagoya City University
3 Ehime University School of Medicine
4 University of Miyazaki
* To whom correspondence should be addressed. E-mail: linxx004{at}tc.umn.edu.
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- 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 upon the external mitogen-related kinase (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.
