Centrioles Shape ERK Signaling Outcomes to Support Lung Branching

Centrioles comprise the heart of centrosomes, where they organize microtubules. To study the function of centrioles in development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from endoderm did not disrupt intestinal growth or development. In contrast, in the lung, loss of centrioles blocked branching. In lung, loss of centrioles led to apoptosis specifically of SOX2-expressing airway epithelial cells. Loss of centrioles also activated p53. Deleting p53 in mice with acentriolar endoderm rescued SOX2+ cell survival, lung branching and viability. To investigate why endoderm-wide p53 activation specifically disrupted SOX2+ cell survival, we measured pro-survival cues. ERK was active specifically in lung cells protected from loss of centrioles and throughout the intestine. Pharmacologically inhibiting ERK activated apoptosis in acentriolar cells, revealing that ERK activity protects acentriolar cells from apoptosis. These findings reveal that the developmental consequences of centriolar defects and p53 activation are shaped by differential ERK activity.