Yu Jeffrey C, Fox Zachary D, Crimp James L, Littleford Hana E, Jowdry Andrea L, Jackman William R
Biology Department, Bowdoin College, Brunswick, Maine.
Dev Dyn. 2015 Apr;244(4):577-90. doi: 10.1002/dvdy.24258. Epub 2015 Mar 17.
Intercellular communication by the hedgehog cell signaling pathway is necessary for tooth development throughout the vertebrates, but it remains unclear which specific developmental signals control cell behavior at different stages of odontogenesis. To address this issue, we have manipulated hedgehog activity during zebrafish tooth development and visualized the results using confocal microscopy.
We first established that reporter lines for dlx2b, fli1, NF-κB, and prdm1a are markers for specific subsets of tooth germ tissues. We then blocked hedgehog signaling with cyclopamine and observed a reduction or elimination of the cranial neural crest derived dental papilla, which normally contains the cells that later give rise to dentin-producing odontoblasts. Upon further investigation, we observed that the dental papilla begins to form and then regresses in the absence of hedgehog signaling, through a mechanism unrelated to cell proliferation or apoptosis. We also found evidence of an isometric reduction in tooth size that correlates with the time of earliest hedgehog inhibition.
We hypothesize that these results reveal a previously uncharacterized function of hedgehog signaling during tooth morphogenesis, regulating the number of cells in the dental papilla and thereby controlling tooth size.
刺猬细胞信号通路介导的细胞间通讯在整个脊椎动物的牙齿发育过程中是必需的，但目前尚不清楚在牙发生的不同阶段，哪些特定的发育信号控制细胞行为。为了解决这个问题，我们在斑马鱼牙齿发育过程中操纵了刺猬信号活性，并使用共聚焦显微镜观察结果。
我们首先确定，dlx2b、fli1、NF-κB和prdm1a的报告基因系是牙胚组织特定亚群的标记物。然后，我们用环杷明阻断刺猬信号，观察到颅神经嵴来源的牙乳头减少或消失，牙乳头通常包含后来产生牙本质的成牙本质细胞。进一步研究发现，在没有刺猬信号的情况下，牙乳头开始形成，然后退化，其机制与细胞增殖或凋亡无关。我们还发现了牙齿大小等比例缩小的证据，这与最早抑制刺猬信号的时间相关。
我们推测，这些结果揭示了刺猬信号在牙齿形态发生过程中一个以前未被描述的功能，即调节牙乳头中的细胞数量，从而控制牙齿大小。
