Contribution of ECM Components to the Control of Stem Cell Behaviour in an Invertebrate Model System

Adult stem cells are established in ‘niches’, specific anatomic locations that regulate how stem cells participate in tissue regeneration and repair. Environmental signals are provided by the niche, which is composed of extracellular component and specialized cell populations located in unique topological relationships with the stem cells in different adult tissues. The extracellular matrix (ECM) represents a key component of the niche. Remodelling of this structure by metalloproteases regulates proliferation, differentiation and migration. The composition of the ECM, its three-dimensional organization and proteolytic remodelling are major determinants of the microenvironmental signalling context that controls cell shape, motility, growth, survival and differentiation. Planarians (Platyhelminthes) represent a versatile and powerful model system well known for regenerative potential, high body plasticity and continuous cell turnover. These characteristics depend on a population of adult stem cells, the neoblasts. Damage or reduction in number of neoblasts deeply affects planarian regeneration and survival. Previous observations indicate that planarian stem cells are surrounded by rich ECM and can migrate in ECM during regeneration and tissue homeostasis, suggesting that the study of this structure may provide important information to understanding how the interactions between stem cells and their niche create the dynamic system necessary to ensure homeostasis and regeneration. I have focused my attention on the ECM class of zinc proteases, named metzincins. The metzincin subgroup of zinc proteases, including matrix metalloproteases (MMPs), astacins and a disintegrin and metalloproteases (ADAMs), play a critical role in cell migration, differentiation and morphogenesis, for example interacting with signalling molecules. I characterized 11 ADAM-, 7 Astacin- and 4 MMP-related genes, identified by bioinformatics analysis of the Schmidtea mediterranea genome. The experimental data obtained in my PhD work provide the first evidence of an involvement of some of these genes in the transmission of environmental signals required for regulation of cell fate and behaviour