Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
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Otros documentos de la autoría: Xie, Chang; Abrams, Shaun; Herranz-Pérez, Vicente; García-Verdugo, Jose Manuel; Reiter, Jeremy
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Título
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activityAutoría
Fecha de publicación
2021-12-20Editor
ElsevierCita bibliográfica
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.Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
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. [-]
Publicado en
Developmental Cell, 2021, vol. 56, no 24Entidad financiadora
National Institutes of Health (NIH) (USA) | Generalitat Valenciana
Código del proyecto o subvención
R01GM095941 | R01AR054396 | R01HD089918 | PROMETEO/2019/075
Derechos de acceso
© 2021 The Author(s). Published by Elsevier Inc.
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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