Serotonin modulates a wide array of neurobehavioral and physiologic processes in mammals, and it has been implicated in the pathophysiology of clinical disorders ranging from primary pulmonary hypertension to irritable bowel syndrome. Yet, the specific cellular and molecular mechanisms underlying the modulatory role of serotonin is still largely obscure, in part due to the multiple receptors and release sites for serotonin, and in part due to the lack of highly specific pharmacologic tools for these receptors. Indeed, serotonin signals thru some 15 receptors, 14 of which are G-Protein Coupled Receptors (GPCRs).

Here, I have used mouse genetic techniques to examine how 5-HT receptors and other similar GPCRs regulate two diverse biological processes: pancreatic islet development and novelty-related behavior. My results suggest that serotonin and Gi-coupled receptor signaling play a critical role in the former by regulating cell division during pancreatic development, and that serotonin and the 5-HT2C receptor play a critical role in the latter by regulating dopamine release in the dorsal striatum. Taken together, these results highlight the wide array of biological processes that are orchestrated by serotonin and its receptors, and they shed light on how evolution has co-opted an ancient neurotransmitter into regulating some of the most complex mammalian physiological and behavioral processes.