Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
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DOI：
10.1016/j.devcel.2014.03.005
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发表时间：
2014-04-14
影响因子：
11.8
通讯作者：
Dai, Xing
中科院分区：
文献类型：
--
作者：
Lee, Briana;Villarreal-Ponce, Alvaro;Fallahi, Magid;Ovadia, Jeremy;Sun, Peng;Yu, Qian-Chun;Ito, Seiji;Sinha, Satrajit;Nie, Qing;Dai, Xing
在上皮组织形态发生过程中，发育的前体细胞经历动态的黏附和细胞骨架重塑，从而触发增殖和迁移。限制这种温和的上皮可塑性以维持承诺的上皮组织中的谱系限制性分化的转录机制还知之甚少。在这里，我们报告同时消融转录抑制因子编码的Ovol1和Ovol2导致胚胎表皮前体细胞的扩张和终末分化受阻。相反，在皮肤上皮细胞中过度表达Ovol2的小鼠表现出早熟分化，伴随着较小的祖细胞隔间。我们发现Ovol1/2缺陷的表皮细胞不能进行α-连环蛋白驱动的肌动蛋白细胞骨架重组和黏附成熟，并表现出类似上皮向间充质转化的变化。值得注意的是，当EMT促进转录因子ZEB1缺失时，这些变化以及有缺陷的末端分化被逆转。总之，我们的发现揭示了OVOL-ZEB1-α-Catenin的顺序抑制，并强调了OVOL通过抑制祖细胞样特征和上皮可塑性而作为上皮黏附和分化的守门人的功能。
During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/2-deficient epidermal cells fail to undertake α-catenin–driven actin cytoskeletal reorganization and adhesive maturation, and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations as well as defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-α-catenin sequential repression and highlight functions of Ovol as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.
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影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe
DOI：
10.1073/pnas.0605333103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Gomis, Roger R.;Alarcon, Claudio;Massague, Joan
通讯作者：
Massague, Joan
影响因子：
6.5
作者：
Diamond, I;Owolabi, T;Glick, A
通讯作者：
Glick, A
影响因子：
23.9
作者：
Lien, Wen-Hui;Guo, Xingyi;Polak, Lisa;Lawton, Lee N.;Young, Richard A.;Zheng, Deyou;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
10.5
作者：
Dai, X;Schonbaum, C;Fuchs, E
通讯作者：
Fuchs, E