Selected publications
Spatiotemporal control of ERK pulse frequency coordinates fate decisions during mammary acinar morphogenesis
Pascal Ender, Paolo Armado Gagliardi, Maciej Dobrzyński, Agne Frismanriene, Coralie Dessauges, Thomas Höhener, Marc-Antoine Jacques, Andrew R. Cohen, Olivier Pertz. Developmental Cell (2022)
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.
Optogenetic actuator/ERK biosensor circuits identify MAPK network nodes that shape ERK dynamics
Coralie Dessauges, Jan Mikelson, Maciej Dobrzyński, Marc-Antoine Jacques, Agne Frismantiene, Paolo Armando Gagliardi, Mustafa Khammash, Olivier Pertz. Molecular Systems Biology (2022)18:e10670
Combining single-cell measurements of ERK activity dynamics with perturbations provides insights into the MAPK network topology. We built circuits consisting of an optogenetic actuator to activate MAPK signaling and an ERK biosensor to measure single-cell ERK dynamics. This allowed us to conduct RNAi screens to investigate the role of 50 MAPK proteins in ERK dynamics. We found that the MAPK network is robust against most node perturbations.
Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
Paolo Armando Gagliardi, Maciej Dobrzyński, Marc-Antoine Jacques, Coralie Dessauges, Pascal Ender, Yannick Blum, Robert M Hughes, Andrew R. Cohen, Olivier Pertz. Developmental Cell (2021)
Cell death events continuously challenge epithelial barrier function yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of extracellular-signal-regulated kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3–4 h. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults.
