Thiery Alexandre P, Standing Ariane S I, Cooper Rory L, Fraser Gareth J
Department of Animal and Plant Sciences, University of Sheffield, Sheffield, United Kingdom.
Department of Craniofacial Development and Stem Cell Biology, King's College London, London, United Kingdom.
Elife. 2022 May 10;11:e73173. doi: 10.7554/eLife.73173.
Development of tooth shape is regulated by the enamel knot signalling centre, at least in mammals. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of , and to the sites of future dental cusps in the shark (), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling developmental phenotypes and cusp shapes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.
牙齿形状的发育至少在哺乳动物中受釉结信号中心调控。在牙齿发育过程中，成纤维细胞生长因子（Fgf）信号调节釉结与相邻牙上皮之间的增殖差异，从而导致牙尖的形成。鉴于信号传导方面的差异，非哺乳动物脊椎动物中是否存在釉结存在争议。在此，我们展示了鲨鱼（）中 、 和 在未来牙尖部位的保守性和局限性，同时也突出了鲨鱼和小鼠之间的显著差异。我们揭示了在经典Wnt信号通路受到小分子干扰后牙齿大小、形状和牙尖数量的变化。由此产生的牙齿表型反映了在哺乳动物中观察到的效应，在哺乳动物中经典Wnt被认为是釉结信号的上游调节因子。鲨鱼牙齿形态发生的计算机模拟表明，激活和抑制信号的细微变化如何改变牙齿形状，类似于在实验性Wnt干扰后观察到的发育表型和牙尖形状。我们的结果支持了整个脊椎动物中类似釉结信号中心的功能保守性，并表明从鲨鱼到哺乳动物的各种牙齿类型遵循相似的发育蓝图。信号传导中的谱系特异性差异不足以反驳这个信号中心的同源性，该信号中心可能比牙齿本身更古老。
