p38-mediated cell growth and survival drive rapid embryonic wound repair

Gordana Scepanovic; Miranda Victoria Hunter; Ran Kafri; Rodrigo Fernandez-Gonzalez

doi:10.1016/j.celrep.2021.109874

p38-mediated cell growth and survival drive rapid embryonic wound repair

Cell Rep. 2021 Oct 19;37(3):109874. doi: 10.1016/j.celrep.2021.109874.

Authors

Gordana Scepanovic¹, Miranda Victoria Hunter¹, Ran Kafri², Rodrigo Fernandez-Gonzalez³

Affiliations

¹ Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada; Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON M5G 1M1, Canada.
² Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada; Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON M5G 1M1, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Electronic address: rodrigo.fernandez.gonzalez@utoronto.ca.

PMID: 34686334
DOI: 10.1016/j.celrep.2021.109874

Abstract

Embryos repair wounds rapidly, with no inflammation or scarring, in a process that involves polarization of the actomyosin cytoskeleton. Actomyosin polarization results in the assembly of a contractile cable around the wound that drives wound closure. Here, we demonstrate that a contractile actomyosin cable is not sufficient for rapid wound repair in Drosophila embryos. We show that wounding causes activation of the serine/threonine kinase p38 mitogen-activated protein kinase (MAPK) in the cells adjacent to the wound. p38 activation reduces the levels of wound-induced reactive oxygen species in the cells around the wound, limiting wound size. In addition, p38 promotes an increase in volume in the cells around the wound, thus facilitating the collective cell movements that drive rapid wound healing. Our data indicate that p38 regulates cell volumes through the sodium-potassium-chloride cotransporter NKCC1. Our work reveals cell growth and cell survival as cell behaviors critical for embryonic wound repair.

Keywords: Drosophila embryo; cell volume; collective cell migration; epithelial morphogenesis; live microscopy; quantitative image analysis; reactive oxygen species; wound healing.

Publication types

Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Animals
Animals, Genetically Modified
Cell Proliferation*
Cell Size
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / embryology
Drosophila melanogaster / enzymology*
Drosophila melanogaster / genetics
Enzyme Activation
Gene Expression Regulation, Developmental
Myosin Type II / metabolism
Oxidative Stress
Reactive Oxygen Species / metabolism
Signal Transduction
Solute Carrier Family 12, Member 2 / genetics
Solute Carrier Family 12, Member 2 / metabolism
Time Factors
Wound Healing*
Wounds and Injuries / enzymology*
Wounds and Injuries / genetics
Wounds and Injuries / pathology
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Drosophila Proteins
Reactive Oxygen Species
Solute Carrier Family 12, Member 2
p38 Mitogen-Activated Protein Kinases
Myosin Type II