title: Requirements for FGF3 and FGF10 during inner ear formation.
abstract: 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.
authors: Center for Molecular Neurobiology Hamburg, University of Hamburg, Falkenried 94, D-20251 Hamburg, Germany.
authors: Yolanda
authors: Y
authors: Alvarez
authors: Maria Teresa
authors: MT
authors: Alonso
authors: Victor
authors: V
authors: Vendrell
authors: Laura Cecilia
authors: LC
authors: Zelarayan
authors: Pablo
authors: P
authors: Chamero
authors: Thomas
authors: T
authors: Theil
authors: Michael R
authors: MR
authors: Bösl
authors: Shigeaki
authors: S
authors: Kato
authors: Mark
authors: M
authors: Maconochie
authors: Dieter
authors: D
authors: Riethmacher
authors: Thomas
authors: T
authors: Schimmang
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D000013:Congenital Abnormalities / Q000235:genetics; D007758:Ear, Inner / Q000196:embryology*; D051526:Fibroblast Growth Factor 10; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D051379:Mice / Q000196:embryology; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014714:Vertebrates / Q000196:embryology*; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins
chemical_list: C489198:FGF3 protein, Xenopus; C496464:Fgf10 protein, mouse; C489197:Fgf3 protein, mouse; D051526:Fibroblast Growth Factor 10; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; D005346:Fibroblast Growth Factors