5-HT2B receptor mediates serotonin morphogenetic signaling during Xenopus laevis eye and craniofacial development

The monoamine serotonin (5-HT), is a well-known neurotransmitter that influences a wide variety of central and peripheral functions in the adult organism. Increasing experimental evidences demonstrated that 5-HT plays also an important role in morphogenesis by modulating processes such as gastrulation, craniofacial and bone patterning and the generation of the left-right asymmetry, as well as in neural development and plasticity. Among 5-HT receptors, 5-HT2B is expressed during CNS, heart and craniofacial development. By using Xenopus laevis as a model system, our research group previously demonstrated that 5-HT2B receptor is expressed in the proliferative region of the retina and the neural tube and that 5-HT2B loss of function results in abnormal eye morphology due to a decrease in the proliferation rate of retinoblasts and an increase of the apoptotic rate of retinal cells. In order to further investigate the role of 5-HT2B in eye development, during the first part of my PhD program, I performed complementary gene gain of function experiments. I found that 5-HT2B over-expression resulted in the formation of eyes with irregular form, position and orientation and showing defects in the optic fissure closure and in the pigmented epithelium formation. A detailed molecular analysis also revealed a disorganization of the typical laminar retinal structure and the presence of differentiated retinal cells in ectopic position. As mouse embryos treated with 5-HT2 antagonists develop severe craniofacial alterations, during the second part of my PhD program, I asked the question whether 5-HT2B receptor signaling could also play a role in craniofacial development. Gene gain and loss of function experiments revealed a direct involvement of 5-HT2B receptor in mediating 5-HT morphogenetic action during craniofacial skeletal development by influencing cranial neural crest cells development.