Vertebrate teeth exhibit a wide range of regenerative systems. Many species, including most mammals, reptiles, and amphibians, form replacement teeth at a histologically distinct location called the successional dental lamina, while other species do not employ such a system. Notably, a ‘lamina-less’ tooth replacement condition is found in a paraphyletic array of ray-finned fishes, such as stickleback, trout, cod, medaka, and bichir. Furthermore, the position, renewal potential, and latency times appear to vary drastically across different vertebrate tooth regeneration systems. The progenitor cells underlying tooth regeneration thus present highly divergent arrangements and potentials. Given the spectrum of regeneration systems present in vertebrates, it is unclear if morphologically divergent tooth regeneration systems deploy an overlapping battery of genes in their naïve dental tissues. In the present work, we aimed to determine whether or not tooth progenitor epithelia could be composed of a conserved cell type between vertebrate dentitions with divergent regeneration systems. To address this question, we compared the pharyngeal tooth regeneration processes in two ray-finned fishes: zebrafish (Danio rerio) and threespine stickleback (Gasterosteus aculeatus). These two teleost species diverged approximately 250 million years ago and demonstrate some stark differences in dental morphology and regeneration. Here, we find that the naïve successional dental lamina in zebrafish expresses a battery of nine genes (bmpr1aa, bmp6, cd34, gli1, igfbp5a, lgr4, lgr6, nfatc1, and pitx2), while active Wnt signaling and Lef1 expression occur during early morphogenesis stages of tooth development. We also find that, despite the absence of a histologically distinct successional dental lamina in stickleback tooth fields, the same battery of nine genes (Bmpr1a, Bmp6, CD34, Gli1, Igfbp5a, Lgr4, Lgr6, Nfatc1, and Pitx2) are expressed in the basalmost endodermal cell layer, which is the region most closely associated with replacement tooth germs. Like zebrafish, stickleback replacement tooth germs additionally express Lef1 and exhibit active Wnt signaling. Thus, two fish systems that either have an organized successional dental lamina (zebrafish) or lack a morphologically distinct successional dental lamina (sticklebacks) deploy similar genetic programs during tooth regeneration. We propose that the expression domains described here delineate a highly conserved “successional dental epithelium” (SDE). Furthermore, a set of orthologous genes is known to mark hair follicle epithelial stem cells in mice, suggesting that regenerative systems in other epithelial appendages may utilize a related epithelial progenitor cell type, despite the highly derived nature of the resulting functional organs.

中文翻译：

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独特的牙齿再生系统可部署一系列保守的基因

脊椎动物的牙齿具有广泛的再生系统。许多物种，包括大多数哺乳动物，爬行动物和两栖动物，在组织学上不同的位置上形成了替换牙齿，这些位置被称为连续牙列，而其他物种则没有采用这种系统。值得注意的是，在一种种类繁多的射线鳍鱼类中发现了“无椎板”的牙齿替换状况，这些鱼类包括棘背鱼，鳟鱼，鳕鱼​​，鱼和鱼。此外，位置，更新潜力和潜伏时间似乎在不同的脊椎动物牙齿再生系统中发生了巨大的变化。因此，牙齿再生的祖细胞呈现出高度分散的排列和潜力。鉴于脊椎动物中存在的再生系统，尚不清楚形态不同的牙齿再生系统是否在其幼稚的牙齿组织中部署了一系列重叠的基因。在目前的工作中，我们旨在确定牙齿祖先上皮是否可以由具有不同再生系统的脊椎动物牙列之间的保守细胞类型组成。为了解决这个问题，我们比较了两种有鳍鱼的咽齿再生过程：斑马鱼（Danio rerio）和三棘棘背鱼（Gasterosteus aculeatus）。这两种硬骨鱼物种大约在2.5亿年前就分化了，它们在牙齿的形态和再生方面表现出明显的差异。在这里，我们发现斑马鱼中的幼稚的连续性牙板表达了九个基因的电池（bmpr1aa，bmp6，cd34，gli1，igfbp5a，lgr4，lgr6，nfatc1和pitx2），而活跃的Wnt信号传导和Lef1表达则发生在牙齿发育的早期形态发生阶段。我们还发现，尽管在棘背式齿场中没有组织学上明显不同的演替性椎板，但相同的九种基因（Bmpr1a，Bmp6，CD34，Gli1，Igfbp5a，Lgr4，Lgr6，Nfatc1和Pitx2）表达相同。最基底的内胚层细胞层，这是与牙齿替代物最紧密相关的区域。像斑马鱼一样，棘背替代牙胚还表达Lef1并表现出活跃的Wnt信号传导。因此，两个有组织的连续性牙板（斑马鱼）或缺乏形态学上独特的连续性牙板（棘背鱼）的鱼类系统在牙齿再生过程中会采用相似的遗传程序。我们建议这里描述的表达域描绘了高度保守的“成功牙龈上皮”（SDE）。此外，已知一组直系同源基因在小鼠中标记毛囊上皮干细胞，这表明尽管所得功能器官具有高度衍生的性质，但其他上皮附件中的再生系统也可能利用相关的上皮祖细胞类型。