Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling
Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling
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DOI：
10.1016/j.devcel.2006.05.014
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发表时间：
2006-08-01
影响因子：
11.8
通讯作者：
Martin, Gail R.
中科院分区：
文献类型：
--
作者：
Klein, Ophir D.;Minowada, George;Martin, Gail R.
不像人类有连续的一排牙齿，老鼠只有臼齿和门牙，它们之间被一个叫做牙间隙的无牙区域隔开。虽然牙芽在胚胎间隙中形成，但它们会退化，不会发育成牙齿。在这里，我们确定了Sprouty（Spry）家族的成员，该家族编码成纤维细胞生长因子（FGF）和其他受体酪氨酸激酶信号传导的负反馈调节因子，作为抑制牙间隙发育的基因。我们发现，不同的Sprouty基因部署在不同的组织隔室-上皮细胞和间充质细胞中的Spry 2和Spry 4-以防止牙间隙的形成。我们提供的遗传证据表明，它们的作用是确保牙间隙牙芽通过FGF配体的信号传导是难治的，这些配体存在于该地区，从而防止这些芽参与FGF介导的上皮细胞和间充质之间的双向信号传导，通常维持牙齿发育。
Unlike humans, who have a continuous row of teeth, mice have only molars and incisors separated by a toothless region called a diastema. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. Here, we identify members of the Sprouty (Spry) family, which encode negative feedback regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase signaling, as genes that repress diastema tooth development. We show that different Sprouty genes are deployed in different tissue compartments-Spry2 in epithelium and Spry4 in mesenchyme-to prevent diastema tooth formation. We provide genetic evidence that they function to ensure that diastema tooth buds are refractory to signaling via FGF ligands that are present in the region and thus prevent these buds from engaging in the FGF-mediated bidirectional signaling between epithelium and mesenchyme that normally sustains tooth development.