1) Serotonin (5-HT) as signaling molecule in the embryonic development There is growing evidence that neurotransmitters, before acquiring their specific fuctions in the adult nervous system, behave as growth factors during specific developmental periods regulating the development of neural and non-neural tissues. Serotonin is one of the well known monoamine neurotransmitters mediating a wide variety of physiological effects, both in the central and peripheral adult nervous system. Furthmore, 5-HT plays an important role in human psychiatric disorders. In addition to its well- defined role in neurotransmission, 5-HT has been implicated in early embryogenesis, long before nervous system appears. By using Xenopus laevis as model system we are studying the role of 5-HT and its 5-HT2B and 5-HT2C receptors during embryogenesis. By gain and loss of function experiments we demonstrated that 5-HT/ 5-HT2B signaling is involved in retinal histogenesis and eye morphogenesis by supporting cell proliferation and survival. These data highlight an emerging role for neurotransmitters as cell-extrinsic factors that regulate progenitor cell proliferation and may have implications both regarding the mechanisms of retinal organogenesis as well as pathological conditions leading to retinal dystrophies and other pathologies. Since 5-HT2B and 5-HT2C receptors are expressed in overlapping expression patterns in proliferative regions of the developing Xenopus brain and retina, we are focusing on the role 5-HT2C receptors. Recently, many studies have provided evidences for homo- and heterodimerization of G-coupled receptors (GPCRs). In order to unveil possible homo-and/or heterodimerization of 5-HT2B-2C receptors, in collaboration with Prof. R. Franco of the University of Barcellona (Spain) we are using a combination of biochemical and biophysical (fluorescence resonance energy transfer-FRET) techniques to address this issue. By combining in vivo and in vitro studies we expect to get light on 5-HT2 receptor molecular biology and farmacology during development. Another important aspect we are investigating is the role of the 5-HT/5-HT2B-2C signaling in the migration and differentiation of cranial neural crest cells and their implications in the craniofacial morphogenesis. 2) Extracellular matrix hyaluronan, hyaluronan receptors and proteoglycans: modulation and function in cell migration and differentiation during embryogenesis Hyaluronan (HA) is a crucial glycosaminoglycan of vertebrate extracellular matrix. In dynamic cellular systems, such as embryonic development, tissue regeneration and tumorigenesis, HA has been shown to influence cell behaviour, including cell migration, proliferation and differentiation both by assembling the interstitial matrices and by directly influencing cell behaviour via interaction with signal transducing receptors such as CD44 and RHAMM.We are using Xenopus laevis to study the role of HA and CD44 in vivo during cell migration and differentiation processes. The spatio-temporal gene expression profile of the three known vertebrate hyaluronan synthases (XHas1, XHas2 and XHas3) shows a very close conservation of Xenopus Has genes with that of mammals. Recently, we demonstrated a critical role of XHas2 and XCD44 during muscle formation and precursor muscle cell migration. To further dissect the role of these molecules, on migration and differentiation processes we focused our attention on cranial neural crest cells (NCCs) development. We knocked-down the XHas1, XHas2 and XCD44 gene functions demonstrating that XHas1 and XHas2, in concert with XCD44, are involved in the NCCs migration and that hyaluronan, but not XCD44, is required in post-migratory stages to support cells survival. In order to investigate possible action mechanisms underlying hyaluronan function, we are now exploring the possible functional interaction of hyaluronan with alternative receptors, such as RHAMM, and hyaluronan binding proteins such as the protoglycan versican.
Lab MembershipsOri Lab (Principal Investigator/Director)
Unit of Cellular and developmental Biology
Department of Biology, University of Pisa, Italy
Via Carducci 13, Ghezzano