Requirements for FGF3 and FGF10 during inner ear formation

TLDR

Fibroblast growth factor family members, including FGF3, regulate vertebrate body plan and organogenesis, and FGF3 is expressed in the hindbrain where it has been implicated in inner ear development, with mouse knockouts showing severe otic vesicle defects. The study aims to delineate the specific roles of FGF3 and related FGFs in murine inner ear formation through loss‑ and gain‑of‑function experiments. The authors used ectopic FGF10 expression in the hindbrain and expression profiling to show that FGF10 can induce otic‑like vesicles and that its expression pattern overlaps with FGF3 during inner ear development. Loss of FGF3 alone causes no major inner ear defects, FGF10 mutants show only mild abnormalities, but combined loss of FGF3 and FGF10 produces severely reduced otic vesicles, revealing redundant roles for these FGFs in otic vesicle 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.