Sonic hedgehog regulates otic capsule chondrogenesis and inner ear development in the mouse embryo
Sonic hedgehog regulates otic capsule chondrogenesis and inner ear development in the mouse embryo
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DOI：
10.1006/dbio.2002.0733
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发表时间：
2002-08-15
影响因子：
2.7
通讯作者：
Frenz, DA
中科院分区：
文献类型：
--
作者：
Liu, W;Li, G;Frenz, DA
内耳软骨囊的发育依赖于耳上皮与其周围的周间质之间的相互作用。在这些组织相互作用过程中，耳上皮内源性因子影响下周间质分化形成软骨化耳囊。我们报道了Sonic hedgehog （Shh）蛋白的定位和Shh基因在发育中的小鼠内耳组织中的表达。我们证明在骨膜间质培养中，Shh不能单独启动耳膜软骨形成。然而，当Shh与耳部上皮或耳部上皮源性成纤维细胞生长因子（FGF2）联合加入培养的骨膜间质时，软骨形成显著增强。将Shh反义寡核苷酸（AS）添加到添加了耳部上皮的培养的周期间质中，可降低内源性Shh的水平并抑制间质细胞的软骨生成反应，而将Shh AS处理的培养物添加Shh可使培养物免于软骨生成抑制。我们证明，通过靶向突变使Shh失活会在发育中的内耳及其周围被膜中产生异常。我们的研究结果支持Shh在哺乳动物胚胎发生过程中作为耳囊形成和内耳发育的调节剂的作用。(C) 2002 Elsevier Science （USA）。
Development of the cartilaginous capsule of the inner ear is dependent on interactions between otic epithelium and its surrounding periotic mesenchyme. During these tissue interactions, factors endogenous to the otic epithelium influence the differentiation of the underlying periotic mesenchyme to form a chondrified otic capsule. We report the localization of Sonic hedgehog (Shh) protein and expression of the Shh gene in the tissues of the developing mouse inner ear. We demonstrate in cultures of periotic mesenchyme that Shh alone cannot initiate otic capsule chondrogenesis. However, when Shh is added to cultured periotic mesenchyme either in combination with otic epithelium or otic epithelial-derived fibroblast growth factor (FGF2), a significant enhancement of chondrogenesis occurs. Addition of Shh antisense oligonucleotide (AS) to cultured periotic mesenchyme with added otic epithelium decreases levels of endogenous Shh and suppresses the chondrogenic response of the mesenchyme cells, while supplementation of Shh AS-treated cultures with Shh rescues cultures from chondrogenic inhibition. We demonstrate that inactivation of Shh by targeted mutation produces anomalies in the developing inner ear and its surrounding capsule. Our results support a role for Shh as a regulator of otic capsule formation and inner ear development during mammalian embryogenesis. (C) 2002 Elsevier Science (USA).