FGF/FGFR-2(IIIb) signaling is essential for inner ear morphogenesis

被引:181
作者
Pirvola, U
Spencer-Dene, B
Liang, XQ
Kettunen, I
Thesleff, I
Fritzsch, B
Dickson, C
Ylikoski, J
机构
[1] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland
[2] Univ Helsinki, Dept Otorhinolaryngol, Helsinki 00014, Finland
[3] Imperial Canc Res Fund, Viral Carcinogenesis Lab, London WC2A 3PX, England
[4] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA
关键词
FGFR-2; FGF10; FGF3; gene expression; gene disruption; inner ear development; cochleovestibular neurons;
D O I
10.1523/JNEUROSCI.20-16-06125.2000
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Interactions between FGF10 and the IIIb isoform of FGFR-2 appear to be crucial for the induction and growth of several organs, particularly those that involve budding morphogenesis. We determined their expression patterns in the inner ear and analyzed the inner ear phenotype of mice specifically deleted for the IIIb isoform of FGFR-2. FGF10 and FGFR-2(IIIb) mRNAs showed distinct, largely nonoverlapping expression patterns in the undifferentiated otic epithelium. Subsequently, FGF10 mRNA became confined to the presumptive cochlear and vestibular sensory epithelia and to the neuronal precursors and neurons. FGFR-2(IIIb) mRNA was expressed in the nonsensory epithelium of the otocyst that gives rise to structures such as the endolymphatic and semicircular ducts. These data suggest that in contrast to mesenchymal-epithelial-based FGF10 signaling demonstrated for other organs, the inner ear seems to depend on paracrine signals that operate within the epithelium. Expression of FGF10 mRNA partly overlapped with FGF3 mRNA in the sensory regions, suggesting that they may form parallel signaling pathways within the otic epithelium. In addition, hindbrain-derived FGF3 might regulate otocyst morphogenesis through FGFR-2(IIIb). Targeted deletion of FGFR-2(IIIb) resulted in severe dysgenesis of the cochleovestibular membraneous labyrinth, caused by a failure in morphogenesis at the otocyst stage. In addition to the nonsensory epithelium, sensory patches and the cochleovestibular ganglion remained at a rudimentary stage. Our findings provide genetic evidence that signaling by FGFR-2(IIIb) is critical for the morphological development of the inner ear.
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页码:6125 / 6134
页数:10
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