Primary Cilia Integrate Hedgehog and Wnt Signaling during Tooth Development
Primary Cilia Integrate Hedgehog and Wnt Signaling during Tooth Development
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DOI：
10.1177/0022034514528211
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发表时间：
2014-05-01
影响因子：
7.6
通讯作者：
Helms, J. A.
中科院分区：
文献类型：
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作者：
Liu, B.;Chen, S.;Helms, J. A.
许多纤毛病的临床特征包括牙齿畸形，但这些缺陷是如何产生的尚不清楚。在这里，我们发现牙间质中运动蛋白Kif3a的基因缺失导致牙生成的停滞。在Wnt1(Cre+)Kif3a（fl/fl）胚胎中，门牙完全缺失，磨牙增大。虽然成釉发育和牙本质发育始于磨牙芽，但这两个过程都过早终止。我们证明，牙间质中Kif3a的缺失会导致该组织中Hedgehog信号的缺失和Wnt信号的增加。有缺陷的牙间质随后向牙上皮发出异常信号，这促使上皮中Hedgehog和Wnt反应上调，并导致多次内陷和牙釉质器官扩大。因此，初级纤毛在牙上皮和间质之间整合了Hedgehog和Wnt信号，而这种依赖于纤毛的整合是牙齿正常发育所必需的。
Many ciliopathies have clinical features that include tooth malformations but how these defects come about is not clear. Here we show that genetic deletion of the motor protein Kif3a in dental mesenchyme results in an arrest in odontogenesis. Incisors are completely missing, and molars are enlarged in Wnt1(Cre+)Kif3a(fl/fl) embryos. Although amelogenesis and dentinogenesis initiate in the molar tooth bud, both processes terminate prematurely. We demonstrate that loss of Kif3a in dental mesenchyme results in loss of Hedgehog signaling and gain of Wnt signaling in this same tissue. The defective dental mesenchyme then aberrantly signals to the dental epithelia, which prompts an up-regulation in the Hedgehog and Wnt responses in the epithelia and leads to multiple attempts at invagination and an expanded enamel organ. Thus, the primary cilium integrates Hedgehog and Wnt signaling between dental epithelia and mesenchyme, and this cilia-dependent integration is required for proper tooth development.