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First published online 12 September 2007
doi: 10.1242/dev.006627

Development 134, 3615-3625 (2007)
Published by The Company of Biologists 2007
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Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium

Ekaterina P. Hatch, C. Albert Noyes, Xiaofen Wang, Tracy J. Wright and Suzanne L. Mansour*

Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA.

* Author for correspondence (e-mail: suzi.mansour{at}genetics.utah.edu)

Accepted 27 July 2007

The inner ear, which contains sensory organs specialized for hearing and balance, develops from an ectodermal placode that invaginates lateral to hindbrain rhombomeres (r) 5-6 to form the otic vesicle. Under the influence of signals from intra- and extraotic sources, the vesicle is molecularly patterned and undergoes morphogenesis and cell-type differentiation to acquire its distinct functional compartments. We show in mouse that Fgf3, which is expressed in the hindbrain from otic induction through endolymphatic duct outgrowth, and in the prospective neurosensory domain of the otic epithelium as morphogenesis initiates, is required for both auditory and vestibular function. We provide new morphologic data on otic dysmorphogenesis in Fgf3 mutants, which show a range of malformations similar to those of Mafb (Kreisler), Hoxa1 and Gbx2 mutants, the most common phenotype being failure of endolymphatic duct and common crus formation, accompanied by epithelial dilatation and reduced cochlear coiling. The malformations have close parallels with those seen in hearing-impaired patients. The morphologic data, together with an analysis of changes in the molecular patterning of Fgf3 mutant otic vesicles, and comparisons with other mutations affecting otic morphogenesis, allow placement of Fgf3 between hindbrain-expressed Hoxa1 and Mafb, and otic vesicle-expressed Gbx2, in the genetic cascade initiated by WNT signaling that leads to dorsal otic patterning and endolymphatic duct formation. Finally, we show that Fgf3 prevents ventral expansion of r5-6 neurectodermal Wnt3a, serving to focus inductive WNT signals on the dorsal otic vesicle and highlighting a new example of cross-talk between the two signaling systems.

Key words: Fibroblast growth factor, Mouse mutant, Endolymphatic duct and sac, WNT signaling, Hearing and balance






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