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

doi:10.7554/eLife.73550

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 journal › Article › peer-review

10 Citations (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 language	English
Article number	e73550
Journal	eLife
Volume	11
Early online date	19 Apr 2022
DOIs	https://doi.org/10.7554/eLife.73550
Publication status	Published - 24 May 2022

Bibliographical note

Funding Information:
In memory of Julian Lewis. We are especially grateful to N. Daudet for his scientific and personal support. To the KCL fish facility staff, particularly to J. Glover. We are grateful to Y. Hinits and S. Wilson for sharing reagents. This project was funded by MRC G1000080/1, Royal Society 2010/R1 and Wellcome

Funding Information:
Trust 207630/Z/17/Z to CL; MR was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under awards T32HD055164 and F31HD097957. KB and DF-B were supported by the Francis Crick Institute core funding from CRUK (FC001751), MRC (FC001751), and Wellcome Trust (FC001751); BBSRC BB/S015906/1 to RNK. DECLARATION OF INTERESTS: The authors declare no competing interests.

Keywords

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

ASJC Scopus subject areas

General Neuroscience
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.7554/eLife.73550Licence: CC BY

Cite this

Alhashem, Z., Feldner-Busztin, D., Revell, C., Portillo, M. A. G., Camargo-Sosa, K., Richardson, J., Rocha, M., Gauert, A., Corbeaux, T., Milanetto, M., Argenton, F., Tiso, N., Kelsh, R. N., Prince, V. E., Bentley, K., & Linker, C. (2022). Notch controls the cell cycle to define leader versus follower identities during collective cell migration. eLife, 11, Article e73550. https://doi.org/10.7554/eLife.73550

Alhashem, Z, Feldner-Busztin, D, Revell, C, Portillo, MAG, Camargo-Sosa, K, Richardson, J, Rocha, M, Gauert, A, Corbeaux, T, Milanetto, M, Argenton, F, Tiso, N, Kelsh, RN, Prince, VE, Bentley, K & Linker, C 2022, 'Notch controls the cell cycle to define leader versus follower identities during collective cell migration', eLife, vol. 11, e73550. https://doi.org/10.7554/eLife.73550

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title = "Notch controls the cell cycle to define leader versus follower identities during collective cell migration",

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.",

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

note = "Funding Information: In memory of Julian Lewis. We are especially grateful to N. Daudet for his scientific and personal support. To the KCL fish facility staff, particularly to J. Glover. We are grateful to Y. Hinits and S. Wilson for sharing reagents. This project was funded by MRC G1000080/1, Royal Society 2010/R1 and Wellcome Funding Information: Trust 207630/Z/17/Z to CL; MR was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under awards T32HD055164 and F31HD097957. KB and DF-B were supported by the Francis Crick Institute core funding from CRUK (FC001751), MRC (FC001751), and Wellcome Trust (FC001751); BBSRC BB/S015906/1 to RNK. DECLARATION OF INTERESTS: The authors declare no competing interests. ",

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AU - Feldner-Busztin, Dylan

AU - Revell, Christopher

AU - Portillo, Macarena Alvarez Garcillan

AU - Camargo-Sosa, Karen

AU - Richardson, Joanna

AU - Rocha, Manuel

AU - Gauert, Anton

AU - Corbeaux, Tatianna

AU - Milanetto, Martina

AU - Argenton, Francesco

AU - Tiso, Natascia

AU - Kelsh, Robert N.

AU - Prince, Victoria E.

AU - Bentley, Katie

AU - Linker, Claudia

N1 - Funding Information: In memory of Julian Lewis. We are especially grateful to N. Daudet for his scientific and personal support. To the KCL fish facility staff, particularly to J. Glover. We are grateful to Y. Hinits and S. Wilson for sharing reagents. This project was funded by MRC G1000080/1, Royal Society 2010/R1 and Wellcome Funding Information: Trust 207630/Z/17/Z to CL; MR was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under awards T32HD055164 and F31HD097957. KB and DF-B were supported by the Francis Crick Institute core funding from CRUK (FC001751), MRC (FC001751), and Wellcome Trust (FC001751); BBSRC BB/S015906/1 to RNK. DECLARATION OF INTERESTS: The authors declare no competing interests.

PY - 2022/5/24

Y1 - 2022/5/24

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Rethinking the neural crest – a novel dynamic model of neural crest fate restriction

Rethinking the neural crest – a novel dynamic model of neural crest fate restriction

Cite this

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Rethinking the neural crest – a novel dynamic model of neural crest fate restriction

Rethinking the neural crest – a novel dynamic model of neural crest fate restriction

Cite this