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FGF signaling in inner ear development
Author(s) -
Mansour Suzanne L,
Noyes C Albert,
Li Chaoying,
Wang Xiaofen,
Hatch Ekaterina,
Twigg Stephen R. F.,
WIlkie Andrew O. M.,
Urness Lisa
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.176.1
Subject(s) - fibroblast growth factor , inner ear , biology , microbiology and biotechnology , ectoderm , fgf10 , morphogenesis , cell fate determination , embryonic stem cell , cochlea , embryogenesis , anatomy , embryo , genetics , gene , transcription factor , receptor
Inner ear development proceeds through phases of otic placode induction, otocyst formation and morphogenesis, and cell type specification. FGF signaling plays dosage sensitive roles in all of these processes. Fgfs3 , 8 and 10 have essential roles in mouse otic placode induction. Microarray analysis identified targets of FGF signaling in otic ectoderm. We will discuss progress in determining their roles in otic development. The Fgf genes are also expressed during later phases of otic development, but later roles are obscured in global single and double KO mice by lethality and/or the sequelae to abnormal induction. To achieve temporal and spatial separation of the multiple functions of these signals throughout otic development, we studied embryos carrying various combinations of conditional Fgf alleles inactivated using different CRE drivers. We find that Fgfs3 and 8 provide redundant endodermal otic‐inducing signals. Initially, Fgf3 is required to maintain dorsal otic gene expression and initiate dorsal outgrowth and later, it functions redundantly with Fgf10 to control cochlear outgrowth. Increases in FGF signaling activity can also have adverse developmental consequences. We found that a mouse model of Muenke syndrome (FGFR3 P250R) has significant, predominantly low‐frequency hearing loss. This is accompanied by a cochlear supporting cell fate switch and excess outer hair cell development.