Sonic hedgehog regulates growth and morphogenesis of the tooth.
Sonic hedgehog regulates growth and morphogenesis of the tooth.
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发表时间：
2000-11
期刊：
影响因子：
4.6
通讯作者：
H. R. Dassule;P. Lewis;M. Bei;R. Maas;Andy McMahon
中科院分区：
文献类型：
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作者：
H. R. Dassule;P. Lewis;M. Bei;R. Maas;Andy McMahon
在哺乳动物牙齿发育过程中，口腔外胚层和间质协调生长和分化，形成具有精确形状、大小和功能的器官。牙上皮及其相关的牙间质最初向内生长形成牙芽。接下来，上皮组织折叠形成牙齿形状。与此同时，相邻的上皮细胞和间充质细胞分别分化为分泌珐琅质的成釉细胞和分泌牙本质的成牙细胞。上皮和间质的生长、形态发生和分化是由分泌的信号蛋白协调的。Sonic hedgehog基因（Shh）编码一种信号肽，这种肽在口腔上皮内陷前和牙齿上皮发育过程中存在。我们通过使用条件等位基因在牙齿上皮长入后不久去除Shh活性，研究了Shh在小鼠牙齿发育中的作用。Shh功能的减少和丧失导致帽期牙齿雏形，其形态受到严重破坏。牙齿的整体尺寸减小，舌上皮内陷和牙髓均缺失。然而，牙釉质结，一个假定的冠形成组织者，存在并表达Fgf4， Wnt10b， Bmp2和Lef1，与野生型一样。出生时，牙齿的大小和形状受到严重影响，成釉细胞和成牙层的极性和组织被破坏。然而，牙本质和牙釉质特异性标记都被表达，并产生大量的牙齿特异性细胞外基质。这一观察结果被移植研究证实，在移植研究中，牙齿雏形在肾囊下培养了几天。在这些条件下，牙釉质和牙本质都得到了沉积，尽管牙釉质和牙本质层仍然是无序的。这些研究表明，Shh调节生长并决定牙齿的形状。然而，Shh信号对于成釉细胞或成牙细胞的分化并不是必需的。
During mammalian tooth development, the oral ectoderm and mesenchyme coordinate their growth and differentiation to give rise to organs with precise shapes, sizes and functions. The initial ingrowth of the dental epithelium and its associated dental mesenchyme gives rise to the tooth bud. Next, the epithelial component folds to give the tooth its shape. Coincident with this process, adjacent epithelial and mesenchymal cells differentiate into enamel-secreting ameloblasts and dentin-secreting odontoblasts, respectively. Growth, morphogenesis and differentiation of the epithelium and mesenchyme are coordinated by secreted signaling proteins. Sonic hedgehog (Shh) encodes a signaling peptide which is present in the oral epithelium prior to invagination and in the tooth epithelium throughout its development. We have addressed the role of Shh in the developing tooth in mouse by using a conditional allele to remove Shh activity shortly after ingrowth of the dental epithelium. Reduction and then loss of Shh function results in a cap stage tooth rudiment in which the morphology is severely disrupted. The overall size of the tooth is reduced and both the lingual epithelial invagination and the dental cord are absent. However, the enamel knot, a putative organizer of crown formation, is present and expresses Fgf4, Wnt10b, Bmp2 and Lef1, as in the wild type. At birth, the size and the shape of the teeth are severely affected and the polarity and organization of the ameloblast and odontoblast layers is disrupted. However, both dentin- and enamel-specific markers are expressed and a large amount of tooth-specific extracellular matrix is produced. This observation was confirmed by grafting studies in which tooth rudiments were cultured for several days under kidney capsules. Under these conditions, both enamel and dentin were deposited even though the enamel and dentin layers remained disorganized. These studies demonstrate that Shh regulates growth and determines the shape of the tooth. However, Shh signaling is not essential for differentiation of ameloblasts or odontoblasts.