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

Ender, Pascal; Gagliardi, Paolo Armando; Dobrzyński, Maciej; Frismantiene, Agne; Dessauges, Coralie; Höhener, Thomas; Jacques, Marc-Antoine; Cohen, Andrew R; Pertz, Olivier (2022). Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis. Developmental cell, 57(18), 2153-2167.e6. Elsevier 10.1016/j.devcel.2022.08.008

[img] Text
1-s2.0-S1534580722005949-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (14MB) | Request a copy

The 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 and proliferation. Subsequent decrease in motility correlates with lower ERK pulse frequency and quiescence. Later, during lumen formation, coordinated multicellular ERK waves emerge, correlating with high and low ERK pulse frequencies 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 display increased ERK pulse frequency and inner cell survival. Thus, fate decisions during acinar morphogenesis are coordinated by different spatiotemporal modalities of ERK pulse frequency.

Item Type:

Journal Article (Original Article)


09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Ender, Pascal Peter, Gagliardi, Paolo Armando, Dobrzynski, Maciej, Frismantiene, Agne, Dessauges, Coralie, Höhener, Thomas Christoph, Jacques, Marc-Antoine Frédéric Roméo, Pertz, Olivier


500 Science > 570 Life sciences; biology








Pubmed Import

Date Deposited:

21 Sep 2022 09:31

Last Modified:

20 Oct 2023 14:00

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

3D imaging ERK ERK-KTR MAPK MCF10A PI3K PIK3CA H1407R acini biosensors mammary epithelial cells morphogenesis optogenetics signaling dynamics




Actions (login required)

Edit item Edit item
Provide Feedback