Temporal requirements of MAPK effectors reflect signalling microenvironment heterogeneity during Mesp1 + cardiac progenitor emergence and migration

Abstract During mouse gastrulation, cardiac progenitors arise within dynamic morphogenetic landscapes, yet the mechanisms by which the progenitors integrate this information and respond to it remain unclear. We profiled candidate signalling ligands in wild-type and Mesp1 mutant embryos, which display defective progenitor migration. In Mesp1⁺ progenitors, Fgf and Wnt ligand expression changes over gastrulation, coinciding with the emergence of first and second heart fields (FHF, SHF). This temporal pattern is perturbed in Mesp1 mutants. Signal inhibition studies in embryos, cultured ex utero, reveal a role for intracellular signalling effectors in mediating the proper migration of the cardiac progenitors. We demonstrate that the different branches of the MAPK signalling effectors (p38, ERK, JNK) are required in distinct temporal windows for proper migration. Our findings link the heterogeneous signalling environment of the cardiac fields to stage-specific MAPK requirements, offering insight into how progenitors integrate complex environmental inputs to coordinate fate specification and migration.