Pirvola U, Spencer-Dene B, Xing-Qun L, Kettunen P, Thesleff I, Fritzsch B, Dickson C, Ylikoski J
Institute of Biotechnology and Department of Otorhinolaryngology, University of Helsinki, 00014 Helsinki, Finland.
J Neurosci. 2000 Aug 15;20(16):6125-34. doi: 10.1523/JNEUROSCI.20-16-06125.2000.
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.
FGF10与FGFR - 2的IIIb亚型之间的相互作用似乎对多个器官的诱导和生长至关重要，尤其是那些涉及出芽形态发生的器官。我们确定了它们在内耳中的表达模式，并分析了特异性缺失FGFR - 2的IIIb亚型的小鼠的内耳表型。FGF10和FGFR - 2(IIIb) mRNA在未分化的耳上皮中呈现出不同的、基本不重叠的表达模式。随后，FGF10 mRNA局限于耳蜗和前庭的假定感觉上皮以及神经元前体和神经元。FGFR - 2(IIIb) mRNA在耳囊中产生内淋巴管和半规管等结构的非感觉上皮中表达。这些数据表明，与其他器官中基于间充质 - 上皮的FGF10信号传导不同，内耳似乎依赖于上皮内起作用的旁分泌信号。FGF10 mRNA的表达在感觉区域与FGF3 mRNA部分重叠，表明它们可能在耳上皮内形成平行的信号通路。此外，后脑来源的FGF3可能通过FGFR - 2(IIIb)调节耳囊形态发生。FGFR - 2(IIIb)的靶向缺失导致耳蜗前庭膜迷路严重发育不全，这是由于耳囊阶段形态发生失败所致。除了非感觉上皮外，感觉斑和耳蜗前庭神经节仍处于发育不全阶段。我们的研究结果提供了遗传学证据，表明FGFR - 2(IIIb)信号传导对内耳的形态发育至关重要。
