Notch Controls the Cell Cycle to Define Leader Versus Follower Identities During Collective Cell Migration
Authors
Affiliations
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 G and become followers, while leaders with high Notch activity quickly undergo G/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.
Wu L, Katsube T, Li X, Wang B, Xie Y Front Public Health. 2025; 13:1509675.
PMID: 39980929 PMC: 11839412. DOI: 10.3389/fpubh.2025.1509675.
Leonard-Duke J, Agro S, Csordas D, Bruce A, Eggertsen T, Tavakol T PNAS Nexus. 2024; 4(1):pgae551.
PMID: 39720203 PMC: 11667245. DOI: 10.1093/pnasnexus/pgae551.
Liu X, Pacwa A, Bresciani G, Swierczynska M, Dorecka M, Smedowski A Mol Med. 2024; 30(1):109.
PMID: 39060957 PMC: 11282803. DOI: 10.1186/s10020-024-00875-y.
Leonard-Duke J, Agro S, Csordas D, Bruce A, Eggertsen T, Tavakol T bioRxiv. 2024; .
PMID: 38559112 PMC: 10979947. DOI: 10.1101/2024.03.15.585249.
Increased collective migration correlates with germline stem cell competition in a basal chordate.
Fentress M, De Tomaso A PLoS One. 2023; 18(10):e0291104.
PMID: 37903140 PMC: 10615308. DOI: 10.1371/journal.pone.0291104.