Pirvola Ulla, Zhang Xiuqin, Mantela Johanna, Ornitz David M, Ylikoski Jukka
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
Dev Biol. 2004 Sep 15;273(2):350-60. doi: 10.1016/j.ydbio.2004.06.010.
The mammalian inner ear comprises the cochleovestibular labyrinth, derived from the ectodermal otic placode, and the encasing bony labyrinth of the temporal bone. Epithelial-mesenchymal interactions are thought to control inner ear development, but the modes and the molecules involved are largely unresolved. We show here that, during the precartilage and cartilage stages, Fgf9 is expressed in specific nonsensory domains of the otic epithelium and its receptors, Fgfr1(IIIc) and Fgfr2(IIIc), widely in the surrounding mesenchyme. To address the role of Fgf9 signaling, we analyzed the inner ears of mice homozygous for Fgf9 null alleles. Fgf9 inactivation leads to a hypoplastic vestibular component of the otic capsule and to the absence of the epithelial semicircular ducts. Reduced proliferation of the prechondrogenic mesenchyme was found to underlie capsular hypoplasticity. Semicircular duct development is blocked at the initial stages, since fusion plates do not form. Our results show that the mesenchyme directs fusion plate formation and they give direct evidence for the existence of reciprocal epithelial-mesenchymal interactions in the developing inner ear. In addition to the vestibule, in the cochlea, Fgf9 mutation caused defects in the interactions between the Reissner's membrane and the mesenchymal cells, leading to a malformed scala vestibuli. Together, these data show that Fgf9 signaling is required for inner ear morphogenesis.
哺乳动物的内耳由源自外胚层耳基板的蜗前庭迷路以及颞骨的包绕性骨迷路组成。上皮-间充质相互作用被认为控制着内耳发育，但其中涉及的模式和分子在很大程度上尚未明确。我们在此表明，在软骨前期和软骨阶段，Fgf9在耳上皮的特定非感觉区域表达，而其受体Fgfr1(IIIc)和Fgfr2(IIIc)则在周围间充质中广泛表达。为了探究Fgf9信号传导的作用，我们分析了Fgf9无效等位基因纯合小鼠的内耳。Fgf9失活导致耳囊的前庭部分发育不全，并且上皮半规管缺失。发现软骨前间充质的增殖减少是囊发育不全的基础。半规管发育在初始阶段受阻，因为融合板未形成。我们的结果表明间充质指导融合板形成，并且为发育中的内耳中存在相互的上皮-间充质相互作用提供了直接证据。除前庭外，在耳蜗中，Fgf9突变导致Reissner膜与间充质细胞之间的相互作用出现缺陷，导致前庭阶畸形。总之，这些数据表明Fgf9信号传导是内耳形态发生所必需的。
