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Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis
Journal article   Open access

Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis

Pascal Ender, Paolo Armando Gagliardi, Maciej Dobrzyński, Agne Frismantiene, Coralie Dessauges, Thomas Höhener, Marc-Antoine Jacques, Andrew R. Cohen and Olivier Pertz
23 Nov 2021
PMID: 36167056
url
https://doi.org/10.48350/173037View
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Abstract

Acinar morphogenesis Acinus Apoptosis Cell biology Chemistry MAPK/ERK pathway Motility Optogenetics PIK3CA H1047R Pulse frequency
AbstractThe signaling events controlling proliferation, survival, and apoptosis during mammary epithelial acinar morphogenesis remain poorly characterized. By imaging single-cell ERK activity dynamics in MCF10A acini, we find that these fates depend on the average frequency of non-periodic ERK pulses. High pulse frequency is observed during initial acinus growth, correlating with rapid cell motility. Subsequent decrease in motility correlates with lower ERK pulse frequency and quiescence. Later, during lumen formation, coordinated ERK waves emerge across multiple cells of an acinus, correlating with high and low ERK pulse frequency in outer surviving and inner dying cells respectively. Optogenetic entrainment of ERK pulses causally connects high ERK pulse frequency with inner cell survival. Acini harboring the PIK3CA H1047R mutation, commonly observed in breast cancer, display increased ERK pulse frequency, inner cell survival and loss of lumen formation. Thus, fate decisions during acinar morphogenesis are fine-tuned by different spatio-temporal coordination modalities of ERK pulse frequency.

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Web of Science research areas
Cell Biology
Developmental Biology
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