Mesoderm and mesodermal structures in the sea urchin embryo are entirely generated by two embryologically distinct populations of mesenchyme cells: the primary (PMC) and the secondary (SMC) mesenchyme cells. We have identified the extracellular signal-regulated kinase (ERK) as a key component of the regulatory machinery that controls the formation of both these cell types. ERK is activated in a spatial-temporal manner, which coincides with the epithelial-mesenchyme transition (EMT) of the prospective PMCs and SMCs. Here, we show that ERK controls EMT of both primary and secondary mesenchyme cells. Loss and gain of function experiments demonstrate that ERK signaling is not required for the early specification of either PMCs or SMCs, but controls the maintenance and/or the enhancement of expression levels of regulatory genes which participate in the process of specification of these cell types. In addition, ERK-mediated signaling is essential for the transcription of terminal differentiation genes encoding proteins that define the final structures generated by PMCs and SMCs. Our findings suggest that ERK has a central pan-mesodermal role in coupling EMT and terminal differentiation of all mesenchymal cell types in the sea urchin embryo.