Common developmental pathways link tooth shape to regeneration.
Common developmental pathways link tooth shape to regeneration.
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DOI：
10.1016/j.ydbio.2013.02.007
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发表时间：
2013-05-15
影响因子：
2.7
通讯作者：
Streelman, J. Todd
中科院分区：
文献类型：
--
作者：
Fraser, Gareth J.;Bloomquist, Ryan F.;Streelman, J. Todd
在许多非哺乳类脊椎动物中，成年齿系是由牙齿再生的周期性循环产生的，其中简单的单尖牙被更复杂的形式所取代。因此，与哺乳动物模型相比，大多数脊椎动物的牙齿在替换过程中形成形状。在这里，我们利用马拉维湖慈鲷鱼的牙齿多样性，问脊椎动物一般如何更换他们的牙列，反过来，这个过程如何影响牙齿形态。首先，我们使用免疫组化图表器官发生不断更换慈鲷牙齿，并发现上皮向下生长，通过唇增殖的偏见，启动更换周期。接下来，我们从从头开始，终身牙齿更换和牙齿形态发生过程中活跃的共同途径中确定了一组共表达基因。值得注意的是，我们发现了两种不同的上皮细胞群，表达牙齿能力和细胞潜能的标志物，这可能是牙齿再生的原因。相关基因集同时活跃在假定的信号中心与复杂形状的替代牙齿的分化。最后，我们用小分子在体内操纵靶向通路（BMP、FGF、Hh、Notch、Wnt/β-catenin），并证明了对牙齿替换和牙齿形状的剂量依赖性作用。我们的数据表明，牙齿再生和牙齿形态发生的过程是通过一组共同的分子信号整合的。这种连接随后在哺乳动物牙列中丢失或分离，其中复杂的牙齿形状在第一代牙列中发展，缺乏终身更换的能力。我们对脊椎动物牙齿替换的分子力学的解剖与复杂形状的结合，精确地指出了牙齿发生的各个方面，这些方面可能在实验室中重新进化，以解决再生牙科中的问题。
In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry.
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DOI：
10.1002/jez.b.21254
发表时间：
2009-07-15
影响因子：
2.2
作者：
Boran, Tomas;Peterkova, Renata;Lesot, Herve;Lyons, David B.;Peterka, Miroslav;Klein, Ophir D.
通讯作者：
Klein, Ophir D.
DOI：
10.1387/ijdb.072556cc
发表时间：
2009
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Chang C;Wu P;Baker RE;Maini PK;Alibardi L;Chuong CM
通讯作者：
Chuong CM
影响因子：
4.6
作者：
Ahn, Youngwook;Sanderson, Brian W.;Krumlauf, Robb
通讯作者：
Krumlauf, Robb
影响因子：
4.6
作者：
Cobourne, MT;Miletich, I;Sharpe, PT
通讯作者：
Sharpe, PT
DOI：
10.1073/pnas.1119635109
发表时间：
2012-05-22
影响因子：
11.1
作者：
Fraser, Gareth J.;Britz, Ralf;Smith, Moya M.
通讯作者：
Smith, Moya M.