Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates

PLoS Biol. 2023 Sep 25;21(9):e3002316. doi: 10.1371/journal.pbio.3002316. eCollection 2023 Sep.

Abstract

Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers, or intestinal villi. Here, by imaging mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by 3 hours of rapid and persistent migration followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tissue tension, and are reliant on active WNT secretion. This behaviour disperses mesenchymal cells and allows daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of cell cycle subphase on core mesenchymal behaviour.

Grants and funding

This work was supported by BBSRC awards BB/T007788/1 and BBS/E/D/10002071 received by DJH, and by North West Cancer Research Fund award CR1132, Royal Society award RGS\R2\212427 and Dr. Philip Welch STEM research project funding received by RLM. SRN is supported by a scholarship from the EPSRC Centre for Doctoral Training in Statistical Applied Mathematics at Bath (SAMBa), under the project EP/S022945/1. This research made use of the Balena High Performance Computing (HPC) Service at the University of Bath. CAB is supported by a Carnegie Trust for Scotland PhD studentship. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.