Serotonin (5HT) is a neurotransmitter that mediates a wide variety of effects in the central and peripheral adult nervous system. Experimental evidences demonstrated that serotonin even has an important role as growth and differentiating factor for neuronal and non-neuronal cells by controlling proliferation, migration and apoptosis during development. All the biological actions of 5-HT are mediated by G-coupled receptors and, among these, the 5-HT2B receptor is expressed during CNS, heart and craniofacial development. By using Xenopus laevis as a model system, we demonstrated that 5HT2B receptor loss of function determines a decrease in the proliferation rate of retinoblasts and increases the apoptosis of retinal cells thus resulting in abnormal eye morphology (De Lucchini et al., 2005). In order to further investigate 5HT2B role during development, we performed complementary experiments of gene gain of function. The overexpression of 5HT2B, leads to 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 pointed out a disorganization of the typical laminar retinal structure and the presence of differentiated neuronal cells in ectopic position. Moreover, as pharmacological treatments with 5HT2 antagonists elicited in mice craniofacial alterations, we are studying the formation of craniofacial muscles and skeletal elements in the overexpressing 5HT2B embryos. In particular, 5HT2B gene gain of function results in altered formation of extraocular muscles as well as of the jaw and hyoid cartilages and correlated muscles. Conclusion: We showed that 5HT, via 5HT2B receptor, is among the key extracellular signals that control Xenopus retinal histogenesis and eye morphogenesis. Moreover our results indicate for the first time a direct involvement 5-HT2B receptors in mediating the serotonin action on craniofacial morphogenesis by influencing the formation of skeletal elements and that of the connected muscles.
5-HT2B-mediated serotonin signalling participates in retinal and craniofacial morphogenesis during Xenopus laevis development
DE LUCCHINI, STEFANIA;
2008
Abstract
Serotonin (5HT) is a neurotransmitter that mediates a wide variety of effects in the central and peripheral adult nervous system. Experimental evidences demonstrated that serotonin even has an important role as growth and differentiating factor for neuronal and non-neuronal cells by controlling proliferation, migration and apoptosis during development. All the biological actions of 5-HT are mediated by G-coupled receptors and, among these, the 5-HT2B receptor is expressed during CNS, heart and craniofacial development. By using Xenopus laevis as a model system, we demonstrated that 5HT2B receptor loss of function determines a decrease in the proliferation rate of retinoblasts and increases the apoptosis of retinal cells thus resulting in abnormal eye morphology (De Lucchini et al., 2005). In order to further investigate 5HT2B role during development, we performed complementary experiments of gene gain of function. The overexpression of 5HT2B, leads to 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 pointed out a disorganization of the typical laminar retinal structure and the presence of differentiated neuronal cells in ectopic position. Moreover, as pharmacological treatments with 5HT2 antagonists elicited in mice craniofacial alterations, we are studying the formation of craniofacial muscles and skeletal elements in the overexpressing 5HT2B embryos. In particular, 5HT2B gene gain of function results in altered formation of extraocular muscles as well as of the jaw and hyoid cartilages and correlated muscles. Conclusion: We showed that 5HT, via 5HT2B receptor, is among the key extracellular signals that control Xenopus retinal histogenesis and eye morphogenesis. Moreover our results indicate for the first time a direct involvement 5-HT2B receptors in mediating the serotonin action on craniofacial morphogenesis by influencing the formation of skeletal elements and that of the connected muscles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
