Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
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Title
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activityAuthor (s)
Date
2021-12-20Publisher
ElsevierBibliographic citation
XIE, Chang, et al. Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity. Developmental Cell, 2021, vol. 56, no 24, p. 3334-3348. e6.Type
info:eu-repo/semantics/articleVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
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. Surpr ... [+]
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. [-]
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Developmental Cell, 2021, vol. 56, no 24Funder Name
National Institutes of Health (NIH) (USA) | Generalitat Valenciana
Project code
R01GM095941 | R01AR054396 | R01HD089918 | PROMETEO/2019/075
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© 2021 The Author(s). Published by Elsevier Inc.
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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