Hyaluronan role in Xenopus laevis visceral skeleton morphogenesis

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. 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, during my PhD programme I then focused my attention on cranial neural crest cells (NCCs) development, knocking-down the XHas1, XHas2 and XCD44 gene functions. I showed that the hyaluronan synthases and the hyaluronan receptor present a dynamic expression pattern during cranial NCCs development suggesting multiple roles in the various steps of cranial NCCs migration and differentiation. I demonstrated 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, I started to explore the possible functional interactions of hyaluronan with alternative receptors, such as RHAMM, and hyaluronan binding proteins such as the protoglycan versican. On the whole the presented data demonstrated an unsuspected critical role of hyaluronan in the visceral skeleton morphogenesis and in particular in NCCs migration and differentiation. Moreover I showed for the first time the gene expression pattern of Xversican and XRHAMM in Xenopus laevis opening new working hypothesis that will be further investigated in the near future.