Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

The serotonin receptor 5-HT2B has been shown to be critically important during embryogenesis as the knockout of this gene in mice causes heart defects and embryonic lethality that impairs further analyses on other embryonic cell and tissue types. In the present review we highlight how the use of Xenopus laevis, an alternative vertebrate model suitable for gene loss and gain of function analyses, contributed to our understanding of the role of 5-HT2B signaling during development. In vivo studies showed that the 5-HT2B signaling is not only required for heart development but also has a crucial role in ocular and craniofacial morphogenesis being involved in shaping the first branchial arch and the jaw joint, in the retinogenesis and possibly in the periocular mesenchyme development. These findings may be relevant for our understanding of congenital defects including human birth malformations. In addition, the 5-HT2B appears to be required for the therapeutic actions of selective serotonin reuptake inhibitors commonly prescribed as antidepressant drugs to pregnant and lactating women. We discuss how the understanding of the molecular basis of the serotonin signaling in a suitable animal model embryogenesis may open new lines of investigations and therapies in humans.