Freter Sabine, Muta Yuko, Mak Siu-Shan, Rinkwitz Silke, Ladher Raj K
Laboratory for Sensory Development, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Development. 2008 Oct;135(20):3415-24. doi: 10.1242/dev.026674. Epub 2008 Sep 17.
The development of the vertebrate inner ear is an emergent process. Its progression from a relatively simple disk of thickened epithelium within head ectoderm into a complex organ capable of sensing sound and balance is controlled by sequential molecular and cellular interactions. Fibroblast growth factor (FGF) and Wnt signals emanating from mesoderm and neural ectoderm have been shown to direct inner ear fate. However, the role of these multiple signals during inner ear induction is unclear. We demonstrate that the action of the FGFs and Wnts is sequential, and that their roles support a model of hierarchical fate decisions that progressively restrict the developmental potential of the ectoderm until otic commitment. We show that signalling by Fgf3 and Fgf19 is required to initiate a proliferative progenitor region that is a precursor to both the inner ear and the neurogenic epibranchial placodes. Significantly, we find that only after FGF action is attenuated can the subsequent action of Wnt signalling allow otic differentiation to proceed. In addition, gain and loss of function of Wnt-signalling components show a role for this signalling in repressing epibranchial fate. This interplay of signalling factors ensures the correct and ordered differentiation of both inner ear and epibranchial systems.
脊椎动物内耳的发育是一个涌现过程。它从头部外胚层内相对简单的增厚上皮盘发展成为一个能够感知声音和平衡的复杂器官，这一过程受一系列分子和细胞相互作用的控制。已表明从中胚层和神经外胚层发出的成纤维细胞生长因子（FGF）和Wnt信号可引导内耳命运。然而，这些多种信号在内耳诱导过程中的作用尚不清楚。我们证明FGF和Wnt的作用是相继的，并且它们的作用支持一种分层命运决定模型，该模型逐渐限制外胚层的发育潜能直至耳原基形成。我们表明，Fgf3和Fgf19信号传导是启动一个增殖祖细胞区域所必需的，该区域是内耳和神经源性鳃后体板的前体。重要的是，我们发现只有在FGF作用减弱后，Wnt信号传导的后续作用才能使耳分化得以进行。此外，Wnt信号传导成分的功能获得和丧失表明该信号传导在抑制鳃后体命运方面发挥作用。信号因子之间的这种相互作用确保了内耳和鳃后体系统的正确和有序分化。
