Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea
Development. 2007-07-18; 134(16): 3021-3029
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1. Development. 2007 Aug;134(16):3021-9. Epub 2007 Jul 18.
Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian
Jacques BE(1), Montcouquiol ME, Layman EM, Lewandoski M, Kelley MW.
(1)Section on Developmental Neuroscience, Porter Neuroscience Research Center, 35
Convent Dr, Room 2A-100, National Institute on Deafness and Other Communication
Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
The mammalian auditory sensory epithelium (the organ of Corti) contains a number
of unique cell types that are arranged in ordered rows. Two of these cell types,
inner and outer pillar cells (PCs), are arranged in adjacent rows that form a
boundary between a single row of inner hair cells and three rows of outer hair
cells (OHCs). PCs are required for auditory function, as mice lacking PCs owing
to a mutation in Fgfr3 are deaf. Here, using in vitro and in vivo techniques, we
demonstrate that an Fgf8 signal arising from the inner hair cells is the key
component in an inductive pathway that regulates the number, position and rate of
development of PCs. Deletion of Fgf8 or inhibition of binding between Fgf8 and
Fgfr3 leads to defects in PC development, whereas overexpression of Fgf8 or
exogenous Fgfr3 activation induces ectopic PC formation and inhibits OHC
development. These results suggest that Fgf8-Fgfr3 interactions regulate cellular
patterning within the organ of Corti through the induction of one cell fate (PC)
and simultaneous inhibition of an alternate fate (OHC) in separate progenitor
cells. Some of the effects of both inhibition and overactivation of the
Fgf8-Fgfr3 signaling pathway are reversible, suggesting that PC differentiation
is dependent upon constant activation of Fgfr3 by Fgf8. These results suggest
that PCs might exist in a transient state of differentiation that makes them
potential targets for regenerative therapies.
PMID: 17634195 [Indexed for MEDLINE]