Modulation of tooth regeneration through opposing responses to Wnt and BMP signals in teleosts.

Modulation of tooth regeneration through opposing responses to Wnt and BMP signals in teleosts.
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DOI:
10.1242/dev.202168
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发表时间:
2023-12-01
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
--
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其他
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大多数脊椎动物在成年后都会更换牙齿。这个过程的特点是现有牙齿的脱落和牙齿器官的再生。然而,关于调节牙齿更换的基因回路知之甚少。在这里,我们测试了已知的调节哺乳动物毛发再生的基因的鱼类同源物是否对牙齿替换有影响。研究人员利用三刺棘鱼(Gasterosteus aculeatus)和斑马鱼(Danio rerio)这两种具有不同牙齿再生模式的鱼类,发现四种不同基因的转基因过表达改变了毛发再生模型预测的牙齿置换率:Wnt10a和Grem2a提高了牙齿置换率,而Bmp6和Dkk2强烈抑制了牙齿的形成。因此,与已知的在毛发再生中的作用类似,Wnt和BMP信号分别促进和抑制再生。总牙数的调节与置换率的调节是可分离的。刺鱼牙组织的RNA测序显示,Bmp6过表达导致Wnt抑制剂上调。总之,这些数据支持一个模型,在这个模型中,不同的上皮器官,如牙齿和头发,共享驱动器官再生的遗传电路。摘要:基因过表达实验表明,Wnt和BMP信号在棘鱼和斑马鱼牙齿替换中具有相反的作用,分别对牙齿再生率起正作用和负作用。
Most vertebrate species undergo tooth replacement throughout adult life. This process is marked by the shedding of existing teeth and the regeneration of tooth organs. However, little is known about the genetic circuitry regulating tooth replacement. Here, we tested whether fish orthologs of genes known to regulate mammalian hair regeneration have effects on tooth replacement. Using two fish species that demonstrate distinct modes of tooth regeneration, threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio), we found that transgenic overexpression of four different genes changed tooth replacement rates in the direction predicted by a hair regeneration model: Wnt10a and Grem2a increased tooth replacement rate, whereas Bmp6 and Dkk2 strongly inhibited tooth formation. Thus, similar to known roles in hair regeneration, Wnt and BMP signals promote and inhibit regeneration, respectively. Regulation of total tooth number was separable from regulation of replacement rates. RNA sequencing of stickleback dental tissue showed that Bmp6 overexpression resulted in an upregulation of Wnt inhibitors. Together, these data support a model in which different epithelial organs, such as teeth and hair, share genetic circuitry driving organ regeneration. Summary: Gene overexpression experiments reveal that Wnt and BMP signaling have opposing roles in stickleback and zebrafish tooth replacement, playing positive and negative roles, respectively, on tooth regeneration rates.
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影响因子: 3.3
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发表时间: 1999-12-01
影响因子: --
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