Journal article
Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis
23 Nov 2021
PMID: 36167056
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis
- Creators
- Pascal EnderPaolo Armando GagliardiMaciej DobrzyńskiAgne FrismantieneCoralie DessaugesThomas HöhenerMarc-Antoine JacquesAndrew R. CohenOlivier Pertz
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Electrical and Computer Engineering
- Web of Science ID
- WOS:000870233100001
- Scopus ID
- 2-s2.0-85138467836
- Other Identifier
- 991021811618404721
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- Web of Science research areas
- Cell Biology
- Developmental Biology