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First published online November 17, 2003
doi: 10.1242/10.1242/dev.00881


Development 130, 6329-6338 (2003)
Published by The Company of Biologists 2003


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Requirements for FGF3 and FGF10 during inner ear formation

Yolanda Alvarez1,*, Maria Teresa Alonso1,2,*, Victor Vendrell1,*, Laura Cecilia Zelarayan1, Pablo Chamero1,2, Thomas Theil3, Michael R. Bösl1, Shigeaki Kato4, Mark Maconochie5, Dieter Riethmacher1 and Thomas Schimmang1,{dagger}

1 Center for Molecular Neurobiology Hamburg, University of Hamburg, Falkenried 94, D-20251 Hamburg, Germany
2 Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Departamento de Bioquímica, Biología Molecular y Fisiología, Facultad de Medicina, E-47005 Valladolid, Spain
3 Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
4 Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
5 School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK

{dagger} Author for correspondence (e-mail: schimman{at}epos.zmnh.uni-hamburg.de)

Accepted 23 September 2003

Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.

Key words: Fibroblast growth factor, Otic vesicle, Hindbrain, Mouse




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