The neurotransmitter serotonin, known to regulate neuronal activity and modulate animal behavior, is also present in the embryos of many organisms. However, its developmental role and the underlying molecular mechanism remained unknown for 60 years since its first report in sea urchin embryos in the 1960s. In a study published in Nature Communications, Sanjay Karki and colleagues from Thomas Lecuit’s team report that serotonin and the GPCR serotonin receptors 5HT2A and 5HT2B regulate Myosin-II activity, cell intercalation and tissue flow during Drosophila embryonic axis extension, and dissect the underlying molecular mechanism linking to Rho-Rok-Myosin-II pathway and regulation of receptor activity and turnover by heterodimerization and endocytosis. They report that serotonin signaling forms a quantitative module that regulates the level of Myosin-II activation, while Toll-Cirl forms a polarizing module. Furthermore, they study the primitive streak formation in chick and discover that the mechanical function of serotonin signaling is conserved in birds.