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, has contributed to our understanding of the role of 5-HT2B signaling during development. In vivo studies showed that 5-HT2B signaling is not only required for heart development, but that it also has a crucial role in ocular and craniofacial morphogenesis, being involved in shaping the first branchial arch and the jaw joint, in retinogenesis and possibly in periocular mesenchyme development. These findings may be relevant for our understanding of congenital defects including human birth malformations. In addition, 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 serotonin signaling in a suitable animal embryogenesis model may open new lines of investigations and therapies in humans.
KEY WORDS: 5-HT2B, neural crest cell, eye, craniofacial morphogenesis, SSRISerotonin, an ancient molecule with unsuspected and still unveiled functions Serotonin (5-hydroxytryptamine, 5-HT) is a phylogenetically ancient monoamine that fulfills a broad role in the control of many vital functions including the control of gastrointestinal motility and secretion, cardiovascular regulation, hemostatic processes, the regulation of circadian rhythms, the control of the sleep-wake cycle, memory and learning, perception of pain, appetite and sexual behavior (reviewed by Berger et al., 2009). The broad action of the serotonin signaling system has attracted the interest of researchers in various fields of biology and molecular medicine, spanning from developmental biology, neurobiology to molecular psychiatry. 5-HT is best known for its role in the nervous system where it is one of the neurotransmitters mainly involved in the etiology of various human psychiatric disorders, including anxiety, depression, obsessive-compulsive disorders, schizophrenia, pain and migraine. Accordingly, many substances that interfere with the serotonergic system are commonly used as therapeutic agents. Selective serotonin reuptake inhibitors (SSRIs) are, in fact, the most frequently prescribed drugs for the treatment of depression Int. J. Dev. Biol. 57: 707-714 (2013) Abbreviations used in this paper: 5-HT, serotonin; 5-HTT, serotonin transporter; CNS, central nervous system; CMZ, ciliary marginal zone; Edn1, endothelin 1; GCL, gaglion cell layer; INL, inner nuclear layer; NCCs, neural crest cells; POM, periocular mesenchyme; SSRI, selective serotonin reuptake inhibitors; Tph2, tryptophan hydroxylase 2.and anxiety-related disorders (Berton and Nestler, 2006). These drugs inhibit...