Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN.
Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN.
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DOI：
10.1038/ncb3001
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发表时间：
2014-08
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
不对称细胞分裂允许干细胞平衡增殖和分化。在胚胎发生过程中，小鼠表皮从单层未指明的基底层祖细胞迅速扩张为分层的分化上皮。形态发生涉及垂直（不对称）分裂和纺锤体取向蛋白LGN，但很少有人知道LGN的顶端定位是如何调节的。在这里，我们结合联合收割机传统的遗传学和慢病毒介导的体内RNAi来探索LGN相互作用蛋白Par 3，mInsc和Gαi3的功能。而每个基因单独的损失导致随机化的分裂角度，Gnai 3和mInsc的组合损失导致大部分平面分裂的表型，类似于LGN的损失。这些发现为迄今为止未经测试的模型提供了实验支持，即Par 3-mInsc和Gαi3协同作用以抑制LGN并促进垂直分裂。最后，我们揭示了脱层驱动的早期分层和纺锤体方向依赖性分化之间的发育开关发生在E15左右，揭示了表皮成熟的两步机制。
Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gαi3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3–mInsc and Gαi3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation.
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影响因子：
16.2
作者：
Bultje, Ronald S.;Castaneda-Castellanos, David R.;Jan, Lily Yen;Jan, Yuh-Nung;Kriegstein, Arnold R.;Shi, Song-Hai
通讯作者：
Shi, Song-Hai
影响因子：
9.2
作者：
Hao, Yi;Du, Quansheng;Chen, Xinyu;Zheng, Zhen;Balsbaugh, Jeremy L.;Maitra, Sushmit;Shabanowitz, Jeffrey;Hunt, Donald F.;Macara, Ian G.
通讯作者：
Macara, Ian G.
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
影响因子：
64.8
作者：
Coumailleau, F.;Fuerthauer, M.;Gonzalez-Gaitan, M.
通讯作者：
Gonzalez-Gaitan, M.
影响因子：
4.6
作者：
El-Hashash, Ahmed H. K.;Turcatel, Gianluca;Warburton, David
通讯作者：
Warburton, David