Force coordination distinguishes epithelial and mesenchymal modes of collective chemotaxis.

Collective cell migration is essential for development and tissue homeostasis and plays a central role in pathological processes such as tumor metastasis. While extensively studied in epithelial cells, collective migration is also observed in mesenchymal cells, though the mechanistic similarities and differences between these modes remain unclear. Here, we use neural crest (NC) cells to investigate collective chemotaxis in epithelial and mesenchymal states within the same lineage. Mesenchymal NC clusters migrate collectively toward the chemoattractant SDF-1 through rear-directed contractility of supracellular actomyosin cables and polarized front-edge protrusions. In contrast, epithelial NC cells exhibit polarized cryptic protrusions and increased active Rac1 localization at E-cadherin-mediated junctions. During epithelial chemotaxis, traction forces originate from internal cell-cell junctions, whereas in mesenchymal clusters, they remain peripheral. Our findings reveal that mesenchymal collective chemotaxis relies on supracellular force coordination, while epithelial chemotaxis depends on force generation by individual cells within the collective.