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Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.

Chang Xie | Shaun R Abrams | Vicente Herranz-Pérez | Jose Manuel García-Verdugo | Jeremy F Reiter
Developmental cell | 2021

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 the 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 prosurvival 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.

Pubmed ID: 34932949 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR054396
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE029454
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD089918

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