Notch controls the cell cycle to define leader versus follower identities during collective cell migration

Zain Alhashem, Dylan Feldner-Busztin, Christopher Revell, Macarena Alvarez Garcillan Portillo, Karen Camargo-Sosa, Joanna Richardson, Manuel Rocha, Anton Gauert, Tatianna Corbeaux, Martina Milanetto, Francesco Argenton, Natascia Tiso, Robert N. Kelsh, Victoria E. Prince, Katie Bentley, Claudia Linker

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

Coordination of cell proliferation and migration is fundamental for life, and its dysregulation has catastrophic consequences, such as cancer. How cell cycle progression affects migration, and vice-versa remains largely unknown. We address these questions by combining in-silico modelling and in vivo experimentation in the zebrafish Trunk Neural Crest (TNC). TNC migrate collectively, forming chains with a leader cell directing the movement of trailing followers. We show that the acquisition of migratory identity is autonomously controlled by Notch signalling in TNC. High Notch activity defines leaders, while low Notch determines followers. Moreover, cell cycle progression is required for TNC migration and is regulated by Notch. Cells with low Notch activity stay longer in G1 and become followers, while leaders with high Notch activity quickly undergo G1/S transition and remain in S-phase longer. In conclusion, TNC migratory identities are defined through the interaction of Notch signalling and cell cycle progression.

Original languageEnglish
Article numbere73550
JournaleLife
Volume11
Early online date19 Apr 2022
DOIs
Publication statusPublished - 24 May 2022

Keywords

  • agent-based modelling
  • cell cycle
  • Collective cell migration
  • neural crest
  • Notch
  • zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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