Serotonin Function During Embryonic Development: The 5-HT2B Receptor Contribution

During embryogenesis some neurotransmitters, including serotonin, function as morphogens before being coopted in the central nervous system. Serotonin uptake sites first appear in non-neural tissues such as the heart, the liver, the cranial mesenchyme, the migrating cranial neural crest cells. Serotonin via the 5-HT2B receptor signaling was found as an important regulator of cardiac myocyte differentiation and proliferation of the developing heart acting as a novel survival factor targeting mitochondria in cardiomyocytes. Furthermore, 5-HT2B receptor participates to the differentiation of myeloid precursors for endothelial progenitor cells, facilitates osteoprogenitors recruitment, proliferation and mineralization. The 5-HT2B receptor mRNA was found to be expressed in migratory cranial neural crest cells in mice as well as in Xenopus and zebrafish. The 5-HT2B receptor signaling has a crucial role in neural crest cell derivatives such as the pharyngeal arches and ocular morphogenesis, for shaping the mandibular arch skeletal elements, and is needed to construct a functional buccal skeleton and ocular morphogenesis. Serotonin, by stimulating the 5-HT2B receptor, expressed by crest-derived neuronal progenitors, acts as a growth factor to promote the development of the enteric neurons and stimulates melanocytes proliferation. In this review, we summarize evidence that serotonin via 5-HT2B receptors regulate many important embryological events such as craniofacial and cardiac morphogenesis, including neural crest differentiation, with consequences on eye, skin, and bones.