The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration ‘command’ differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate ‘rightward’ via electrotaxis. Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell–cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell–cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors.
- Award ID(s):
- 2027617
- PAR ID:
- 10437812
- Date Published:
- Journal Name:
- Biochemical Society Transactions
- ISSN:
- 0300-5127
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the Drosophila border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration. Inhibition of Pp1 causes border cells to round up, dissociate, and move as single cells with altered motility. We present evidence that Pp1 promotes proper levels of cadherin-catenin complex proteins at cell-cell junctions within the cluster to keep border cells together. Pp1 further restricts actomyosin contractility to the cluster periphery rather than at individual internal border cell contacts. We show that the myosin phosphatase Pp1 complex, which inhibits non-muscle myosin-II (Myo-II) activity, coordinates border cell shape and cluster cohesion. Given the high conservation of Pp1 complexes, this study identifies Pp1 as a major regulator of collective versus single cell migration.more » « less
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Ribosome biogenesis is critical for the proper production of proteins in cells and has emerged as a regulator of cell invasion and migration in development and in cancer. The Drosophila border cells form a collective that invades and migrates through the surrounding tissue during oogenesis. We previously found that a significant number of ribosome biogenesis genes are differentially expressed from early to late migration stages. Here, we performed a small-scale RNAi screen of a subset of these ribosome genes. Knockdown of seven genes disrupted border cell migration, thus revealing a role for ribosome biogenesis genes in regulating collective cell migration.more » « less
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Abstract Background Collective cell migration underlies many essential processes, including sculpting organs during embryogenesis, wound healing in the adult, and metastasis of cancer cells. At mid-oogenesis,
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Conclusions Overall, our results identified differentially and temporally expressed genetic networks that may facilitate the efficient development and migration of border cells. The genes identified here represent a wealth of new candidates to investigate the molecular nature of dynamic collective cell migrations in developing tissues.
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1042/BST20221202
