Biological Sciences Division
Published April 19, 2022 | Version v1
Journal article Open

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

Creators

  • 1. King's College London
  • 2. Francis Crick Institute
  • 3. University of Bath
  • 4. University of Chicago
  • 5. University of Padova

Description

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.

Data availability

The model code is accessible at https://github.com/Bentley-Cellular-Adaptive-Behaviour-Lab/NeuralCrestCpp, (copy archived at swh:1:rev:cdf63f3786390fb7905092717456cc69f5657ddc). The code used to perform the LDA analysis is accessible in the supplementary files. All numerical data used in the figures is accessible in the supplementary data source file.

Files

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Additional details

Identifiers

DOI
10.7554/eLife.73550
Other
oai:uchicago.tind.io:9840

Related works

Cites
https://doi.org/10.1101/2021.05.27.445572 (URL)

Funding

Medical Research Council
G1000080/1
Royal Society
2010/R1
Wellcome Trust
207630/Z/17/Z
Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institutes of Health
T32HD055164
Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institutes of Health
F31HD097957
Cancer Research UK
FC001751
Medical Research Council
FC001751
Wellcome Trust
FC001751
Biotechnology and Biological Sciences Research Council
BB/S015906/1

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Development, Regeneration, and Stem Cell Biology, Organismal Biology and Anatomy