Early epithelial signaling center governs tooth budding morphogenesis.
Early epithelial signaling center governs tooth budding morphogenesis.
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DOI：
10.1083/jcb.201512074
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发表时间：
2016-09-12
期刊：
影响因子：
--
通讯作者：
Mikkola ML
中科院分区：
文献类型：
--
作者：
Ahtiainen L;Uski I;Thesleff I;Mikkola ML
器官发生是由专门的细胞群，信号中心。它们的分子调控是众所周知的，但涉及的细胞行为仍然不明确。在这里，Ahtiainen等人使用胚胎小鼠牙齿的实时成像来揭示驱动上皮内陷的细胞机制。在器官发生过程中，细胞命运的规范和模式是由信号中心，专门的形态发生表达细胞的集群。在许多器官中，发育的起始是以芽的形成为标志的，但所涉及的细胞机制尚不清楚。在这里，我们使用小鼠切牙作为模型来研究萌芽形态发生。我们发现，一组非增殖上皮细胞出现在早期牙齿原基，并确定这些细胞作为一个信号中心。组织外植体的共聚焦活体成像显示，尽管这些细胞动态重组，但它们不会重新进入细胞周期或促进牙芽的生长。相反，出芽是由相邻细胞的增殖驱动的。我们证明了外胚层发育不良/Edar/核因子κB通路的活性仅限于信号中心，其失活导致更少的静止细胞和更小的芽。这些数据在功能上将信号中心的大小与器官大小联系起来，并暗示早期信号中心是萌芽形态发生的先决条件。
Organogenesis is regulated by specialized clusters of cells, the signaling centers. Their molecular regulation is well known, but the cellular behaviors involved remain ill defined. Here, Ahtiainen et al. use live imaging of embryonic mouse teeth to unveil cellular mechanisms driving epithelial invagination. During organogenesis, cell fate specification and patterning are regulated by signaling centers, specialized clusters of morphogen-expressing cells. In many organs, initiation of development is marked by bud formation, but the cellular mechanisms involved are ill defined. Here, we use the mouse incisor tooth as a model to study budding morphogenesis. We show that a group of nonproliferative epithelial cells emerges in the early tooth primordium and identify these cells as a signaling center. Confocal live imaging of tissue explants revealed that although these cells reorganize dynamically, they do not reenter the cell cycle or contribute to the growing tooth bud. Instead, budding is driven by proliferation of the neighboring cells. We demonstrate that the activity of the ectodysplasin/Edar/nuclear factor κB pathway is restricted to the signaling center, and its inactivation leads to fewer quiescent cells and a smaller bud. These data functionally link the signaling center size to organ size and imply that the early signaling center is a prerequisite for budding morphogenesis.
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DOI：
10.1073/pnas.0607289103
发表时间：
2006-12-05
影响因子：
11.1
作者：
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发表时间：
2009-06-15
影响因子：
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作者：
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