Reciprocal mechanochemical feedback couples neural crest migration and neurulation

Abstract

Cephalic neurulation and neural crest migration are defining morphogenetic events of vertebrate head development. Although traditionally viewed as independent tissue-autonomous programs, their striking spatiotemporal overlap suggests functional coupling. Here, we show that these processes are linked by reciprocal mechanochemical feedback. We find that collective neural crest migration is essential for neural tube closure. As neural crest cells delaminate and invade the surrounding mesoderm, they remodel fibronectin at the neural crest-neural plate interface, creating a specialized extracellular matrix that both separates the two tissues and promotes neural tube morphogenesis by enabling radial intercalation and apical constriction of neural plate cells. This extracellular matrix remodeling requires neural crest-specific expression of the membrane-bound metalloproteinase MMP14. Conversely, neural tube morphogenesis drives neural crest migration. Mechanical compression generated during neural plate bending induces MMP14 expression in neural crest cells, triggering extracellular matrix remodeling that feeds back to facilitate neural tube closure. Together, our findings reveal that neurulation and neural crest migration are not independent morphogenetic programs but components of a self-reinforcing mechanochemical circuit that coordinates vertebrate head morphogenesis.