Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Korea.
Development. 2011 May;138(9):1807-16. doi: 10.1242/dev.056051. Epub 2011 Mar 29.
Each vertebrate species displays specific tooth patterns in each quadrant of the jaw: the mouse has one incisor and three molars, which develop at precise locations and at different times. The reason why multiple teeth form in the jaw of vertebrates and the way in which they develop separately from each other have been extensively studied, but the genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of the key signaling molecules involved in the spatial patterning of teeth and other ectodermal organs such as hair, vibrissae and feathers. Sostdc1, a secreted inhibitor of the Wnt and Bmp pathways, also regulates the spatial patterning of teeth and hair. Here, by utilizing maternal transfer of 5E1 (an anti-Shh antibody) to mouse embryos through the placenta, we show that Sostdc1 is downstream of Shh signaling and suggest a Wnt-Shh-Sostdc1 negative feedback loop as a pivotal mechanism controlling the spatial patterning of teeth. Furthermore, we propose a new reaction-diffusion model in which Wnt, Shh and Sostdc1 act as the activator, mediator and inhibitor, respectively, and confirm that such interactions can generate the tooth pattern of a wild-type mouse and can explain the various tooth patterns produced experimentally.
老鼠有一个门齿和三个臼齿，它们在精确的位置和不同的时间发育。脊椎动物颌骨中形成多颗牙齿的原因以及它们彼此分开发育的方式已经得到了广泛的研究，但控制牙齿空间模式形成的遗传机制仍有待阐明。Sonic hedgehog（Shh）是参与牙齿和其他外胚层器官（如毛发、触须和羽毛）空间模式形成的关键信号分子之一。Sostdc1 是 Wnt 和 Bmp 途径的一种分泌抑制剂，也调节牙齿和毛发的空间模式形成。在这里，我们通过利用胎盘将 5E1（一种抗 Shh 抗体）从母体转移到小鼠胚胎中，表明 Sostdc1 是 Shh 信号的下游，并提出了一个 Wnt-Shh-Sostdc1 负反馈回路，作为控制牙齿空间模式形成的关键机制。此外，我们提出了一个新的反应扩散模型，其中 Wnt、Shh 和 Sostdc1 分别作为激活剂、介体和抑制剂，证实了这种相互作用可以产生野生型小鼠的牙齿模式，并可以解释实验中产生的各种牙齿模式。
