Fgf signaling regulates development and transdifferentiation of hair cells and supporting cells in the basilar papilla.

Abstract:

:The avian basilar papilla (BP) is a likely homolog of the auditory sensory epithelium of the mammalian cochlea, the organ of Corti. During mammalian development Fibroblast growth factor receptor-3 (Fgfr3) is known to regulate the differentiation of auditory mechanosensory hair cells (HCs) and supporting cells (SCs), both of which are required for sound detection. Fgfr3 is expressed in developing progenitor cells (PCs) and SCs of both the BP and the organ of Corti; however its role in BP development is unknown. Here we utilized an in vitro whole organ embryonic culture system to examine the role of Fgf signaling in the developing avian cochlea. SU5402 (an antagonist of Fgf signaling) was applied to developing BP cultures at different stages to assay the role of Fgf signaling during HC formation. Similar to the observed effects of inhibition of Fgfr3 in the mammalian cochlea, Fgfr inhibition in the developing BP increased the number of HCs that formed. This increase was not associated with increased proliferation, suggesting that inhibition of the Fgf pathway leads to the direct conversion of PCs or supporting cells into HCs, a process known as transdifferentiation. This also implies that Fgf signaling is required to prevent the conversion of PCs and SCs into HCs. The ability of Fgf signaling to inhibit transdifferentiation suggests that its down-regulation may be essential for the initial steps of HC formation, as well as for the maintenance of SC phenotypes.

journal_name

Hear Res

journal_title

Hearing research

authors

Jacques BE,Dabdoub A,Kelley MW

doi

10.1016/j.heares.2012.04.018

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

27-39

issue

1-2

eissn

0378-5955

issn

1878-5891

pii

S0378-5955(12)00104-9

journal_volume

289

pub_type

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