Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration, Gap Closure and Organ sculpting by Contact-Mesenchymalization

bioRxiv [Preprint]. 2024 Oct 11:2024.10.10.617649. doi: 10.1101/2024.10.10.617649.

Abstract

Cell behavior emerges from the intracellular distribution of properties like protrusion, contractility and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture - orchestrating self-regulation during development, wound healing, and cancer progression. The new Drosophila testis-nascent-myotube-system allows dissection of contact-dependent migration in vivo at high resolution. Here, we describe a process driving gap-closure during migration: Contact-mesenchymalization via the axon guidance factor Plexin A. This is crucial for testis myotubes to migrate as a continuous sheet, allowing normal sculpting-morphogenesis. Cells must stay filopodial and dynamically ECM-tethered near cell-cell contacts to spread while collectively moving. Our data suggest Semaphorin 1B acts as a Plexin A antagonist, fine-tuning activation. Our data reveal a contact-dependent mechanism to maintain sheet-integrity during migration, driving organ-morphogenesis using a highly conserved pathway. This is relevant for understanding mesenchymal organ-sculpting and gap-closure in migratory contexts like angiogenesis.

Keywords: Axon Guidance; Collective Cell Migration; Contact Inhibition of Locomotion; Contact Stimulation of Migration; Filopodial Migration; Organ Sculpting; Plexin-Semaphorin Signaling.

Publication types

  • Preprint