Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization
Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization
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DOI：
10.1242/dev.00100
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Gritli-Linde, A;Bei, M;McMahon, AP
Sonic hedgehog（Shh）是哺乳动物Hedgehog（Hh）家族的成员之一，在胚胎发生和器官形成过程中起着重要作用。牙齿的发育，即牙齿的发生，是由上皮-间充质相互作用控制的。从牙齿上皮细胞（牙齿发育期间Shh的唯一来源）遗传去除Shh活性改变牙齿上皮细胞和牙齿间充质两者内的牙齿生长和细胞学组织。在该模型中，尚不清楚表型的哪些方面是Shh对靶组织的直接作用的结果，哪些是由于上皮和间充质组分之间相互信号传导的缺陷而引起的间接作用。为了区分这两种替代方案，并扩展我们对Shh在牙形成中的作用的理解，我们使用Cre-loxP系统来去除牙上皮中的Smoothened（Smo）活性。Smo是一种七次通过的膜蛋白，对所有Hh信号的转导都是必需的。因此，从牙上皮中去除Smo活性应该阻断牙上皮衍生物内的Shh信号传导，同时保留正常的间充质信号传导。在这里，我们表明，Shh依赖的相互作用发生在牙齿上皮本身。牙齿间充质发育正常，直到出生。相比之下，牙上皮衍生物显示出改变的增殖、生长、分化和极化。我们的方法揭示了Shh在控制上皮细胞大小、细胞器发育和极化中的作用。此外，我们提供的证据表明，成釉细胞和上层中间层之间的Shh信号可能涉及Patched 2和Gli 1 mRNA的亚细胞定位，这两者都是Shh信号在这些细胞中的靶点。
Sonic hedgehog (Shh), a member of the mammalian Hedgehog (Hh) family, plays a key role during embryogenesis and organogenesis. Tooth development, odontogenesis, is governed by sequential and reciprocal epithelial-mesenchymal interactions. Genetic removal of Shh activity from the dental epithelium, the sole source of Shh during tooth development, alters tooth growth and cytological organization within both the dental epithelium and mesenchyme of the tooth. In this model it is not clear which aspects of the phenotype are the result of the direct action of Shh on a target tissue and which are indirect effects due to deficiencies in reciprocal signalings between the epithelial and mesenchymal components. To distinguish between these two alternatives and extend our understanding of Shh's actions in odontogenesis, we have used the Cre-loxP system to remove Smoothened (Smo) activity in the dental epithelium. Smo, a seven-pass membrane protein is essential for the transduction of all Hh signals. Hence, removal of Smo activity from the dental epithelium should block Shh signaling within dental epithelial derivatives while preserving normal mesenchymal signaling. Here we show that Shh-dependent interactions occur within the dental epithelium itself. The dental mesenchyme develops normally up until birth. In contrast, dental epithelial derivatives show altered proliferation, growth, differentiation and polarization. Our approach uncovers roles for Shh in controlling epithelial cell size, organelle development and polarization. Furthermore, we provide evidence that Shh signaling between ameloblasts and the overlying stratum intermedium may involve subcellular localization of Patched 2 and Gli1 mRNAs, both of which are targets of Shh signaling in these cells.