Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.
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DOI：
10.1016/j.devcel.2021.11.020
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发表时间：
2021-12-20
影响因子：
11.8
通讯作者：
Reiter JF
中科院分区：
文献类型：
--
作者：
Xie C;Abrams SR;Herranz-Pérez V;García-Verdugo JM;Reiter JF
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from endoderm did not disrupt intestinal growth or development, but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a pro-survival cue. ERK was active throughout the intestine and in the distal lung buds, correlating with tolerance to centriole loss. Pharmacologically inhibiting ERK activated apoptosis in acentriolar cells, revealing that ERK activity protects acentriolar cells from apoptosis. Therefore, centrioles are largely dispensable for endodermal growth and the spatial distribution of ERK activity in the endoderm shapes the developmental consequences of centriolar defects and p53 activation. Chang et al. show that endoderm centrioles are dispensable for intestinal development but essential for lung branching. Throughout both intestine and lung loss of centrioles activates p53, but the lack of centrioles induces apoptosis only in domains of low ERK signaling.
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影响因子：
4.3
作者：
Abdelhamed ZA;Natarajan S;Wheway G;Inglehearn CF;Toomes C;Johnson CA;Jagger DJ
通讯作者：
Jagger DJ
影响因子：
14.8
作者：
Chaikuad A;Tacconi EM;Zimmer J;Liang Y;Gray NS;Tarsounas M;Knapp S
通讯作者：
Knapp S
影响因子：
16.6
作者：
Alanis, Denise Martinez;Chang, Daniel R.;Akiyama, Haruhiko;Krasnow, Mark A.;Chen, Jichao
通讯作者：
Chen, Jichao
DOI：
10.1073/pnas.1400568111
发表时间：
2014-04-15
影响因子：
11.1
作者：
Bazzi, Hisham;Anderson, Kathryn V.
通讯作者：
Anderson, Kathryn V.
影响因子：
2.9
作者：
Brown, Roy C.;Lemmon, Betty E.
通讯作者：
Lemmon, Betty E.