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Left/right asymmetric collective migration of parapineal cells is mediated by focal FGF signaling activity in leading cells
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Edité par CCSD ; National Academy of Sciences -
International audience. The ability of cells to collectively interpret surrounding environmental signals underpins their capacity to coordinate their migrationin various contexts, including embryonic development and cancer metastasis. One tractable model for studying collectivemigration is the parapineal, a left-sided group of neurons that arises from bilaterally positioned precursors that undergo acollective migration to the left side of the brain. In zebrafish, the migration of these cells requires Fgf8 and, in this study, we resolvehow FGF signaling correlates with—and impacts the migratory dynamics of—the parapineal cell collective. The temporal and spatialdynamics of an FGF reporter transgene reveal that FGF signaling is activated in only few parapineal cells usually located at theleading edge of the parapineal during its migration. Overexpressing a constitutively active Fgf receptor compromises parapinealmigration in wild-type embryos, while it partially restores both parapineal migration and mosaic expression of the FGF reportertransgene in fgf8−/− mutant embryos. Focal activation of FGF signaling in few parapineal cells is sufficient to promote the migrationof the whole parapineal collective. Finally, we show that asymmetric Nodal signaling contributes to the restriction and leftwards biasof FGF pathway activation. Our data indicate that the first overt morphological asymmetry in the zebrafish brain is promoted byFGF pathway activation in cells that lead the collective migration of the parapineal to the left. This study shows that cell-state differencesin FGF signaling in front versus rear cells is required to promote migration in a model of FGF-dependent collective migration.
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