RECENT DISCOVERIES ON SEROTONIN DEVELOPMENTAL FUNCTIONS: WHAT WE LEARNED FROM XENOPUS

Serotonin (5-HT) is an ancient molecule that appeared very early in evolution and is present in different phyla. The 5-HT signaling system is widely conserved, so researches in different animal models have general relevance for all vertebrates, including humans. 5-HT is implicated in an astonishing number of biological processes and therefore attracted studies in different fields, from neurobiology to developmental biology and neuropsychiatry. 5-HT is present in the egg and in the placenta, which can synthesize it from maternally derived tryptophan and has a key role as a morphogen in several complex networks during development before it can act as a neurotransmitter. Recent advances on how serotonin signaling can influence early development come from Xenopus, thanks to several advantages over other model systems such as rodents. Xenopus studies highlight the role of 5-HT in establishing the left-right asymmetry. These findings have relevance in molecular medicine because a common class of birth defects is due to laterality errors. Recent advances also show that 5-HT is critically required for craniofacial and eye morphogenesis. In particular, 5-HT signaling is necessary for the correct development of the first branchial arch derivatives, and to define and sustain the gene expression network necessary for the jaw and jaw joint formation, which is one of the major novelties of vertebrates. On the other hand, craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, aesthetic, and social consequences. Of all the babies born with birth defects, approximately one-third display anomalies of the head and face. For these reasons the possibility to modulate selectively the activity of the only serotonin receptor expressed in branchial arches (5-HT2B) could be a fascinating possibility for future therapeutical approaches. In conclusion, studies in Xenopus can add a solid background of knowledge that, combined with other approaches, help contributing to the big picture of deciphering the complex roles of serotonin in development.