Matrizes Extracelulares

Interesse da Investigação

Cells within all multicellular organisms are surrounded by a heterogeneous mixture of macromolecules, called the extracellular matrix (ECM). This matrix is synthesised and organised by the cells, providing them with a substrate to interact with and spaces to migrate through. Apart from this structural role, the ECM can also directly influence cell behaviour. It serves as a reservoir for growth factors that in turn influence cell behaviour and it also binds to specific ECM receptors (most commonly integrins) on the cell surface, thus directly affecting processes such as proliferation, differentiation, apoptosis, cytoskeletal remodelling and migration. Our group studies how cell-ECM interactions contribute to vertebrate somite formation and the development of one of the somite derivatives, namely skeletal muscle. Extensive cell rearrangements occur during the formation and differentiation of somites and, at the same time, the composition of the ECM surrounding somitic cells changes. Very little is known about what factors control this ECM turnover and even less is know about how this ever-changing ECM influences the differentiation state, the shape and the locomotive behaviour of the cell it interacts with. Moreover, although knowledge of how paracrine signalling and transcription factors control the patterning of somites is now advanced, almost nothing is known about how they regulate, and are regulated by, the ECM and ECM receptor mediated signalling.

Membros do Grupo

Projecto de Investigação

More than putting cells into place during development: cell-extracellular matrix interactions in myogenesis

Skeletal muscle progenitor cells are one of the derivatives of the epithelial somites. We are studying the role of the extracellular matrix in the process of early muscle cell specification, migration and morphogenesis. Cells interact with their surrounding extracellular matrix via specific cell surface receptors, the best studied belonging to the integrin family of cell surface glycoproteins. Thus, we are interested in how integrin occupation and signaling contributes towards the differentiation and morphogenesis of early skeletal muscle in the embryo.

Funding

PTDC/BIA-BCM/67437/2006
Sólveig Thorsteinsdóttir

Colaboradores

University of Otago, Dunedin, New Zealand
We are collaborating with Marilyn J. Duxson
Pasteur Institute, Paris, France
We are collaborating with Margaret Buckingham.
Netherlands Cancer Institute, Amsterdam, The Netherlands
We are collaborating with Arnoud Sonnenberg

Projecto de Investigação

Changing extracellular matrix networks as regulators of transitions between epithelial and mesenchymal fates during embryogenesis.

Somites are the basis of the segmental pattern of the vertebrate body. They are transient mesodermal segments that, through mesenchyme-to-epithelium and epithelium-to-mesenchyme transitions (MET and EMT) provide the foundations for the segmented organization of our axial skeleton and give rise to the skeletal muscle precursors of trunk and limbs. In this project we aim to unveil the importance of two different ECM networks, the fibrillar fibronectin matrix and the sheet-like laminin matrix, in the regulation of epithelial versus mesenchymal fates during somite development. With this work we hope to significantly contribute to our understanding of somite development in particular and embryonic METs and EMTs in general. Furthermore, since EMT-like transitions occur in metastatic cancers and transitions similar to EMTs (mesenchymal-epithelial reverting transitions or MErTs) are known to lead to integration of metastatic cells into normal tissues our results may also provide a conceptual basis for better addressing these cancer transformations.

Funding

PTDC/SAU-OBD/103771/2008
Sólveig Thorsteinsdóttir

Colaboradores

Pasteur Institute, Paris, France
We are collaborating with Margaret Buckingham.

Netherlands Cancer Institute, Amsterdam, The Netherlands
We are collaborating with Arnoud Sonnenberg

Publicações

Selected June (2010).

Sato T., Rocancourt D., Marques L., Thorsteinsdóttir S. & Buckingham M. (2010). A Pax3/Dmrt2/Myf5 regulatory cascade functions at the onset myogenesis. PLoS Genetics 6(4) :e1000897 Link

Martins G.G., Rifes P., Amândio R., Rodrigues G., Palmeirim I. & Thorsteinsdóttir S. (2009). Dynamic 3D cell rearrangements guided by a fibronectin matrix underlie somitogenesis PLoS ONE 4(10) :e7429 Link

Anderson C., Thorsteinsdóttir S. & Borycki A.-G. (2009). Sonic hedgehog-dependent synthesis of Laminin α1 controls basement membrane assembly in the myotome Development 136 :3495-3504

Fournier-Thibault C., Blavet C., Jarov A., Bajanca F., Thorsteinsdóttir S. & Duband J.-L. (2009). Sonic hedgehog regulates integrin activity, cadherin contacts and cell polarity to orchestrate neural tube morphogenesis Journal of Neuroscience 29 :12506-12520

Thorsteinsdóttir S., Rodrigues G. & Crespo E.G. (2009). Teaching and research on Developmental Biology in Portugal International Journal of Developmental Biology 53 :1235-1243

Rifes, P.*, Carvalho, L.*, Lopes, C., Andrade, R., Rodrigues, G., Palmeirim, I. & Thorsteinsdóttir, S. (2007). Redefining the role of ectoderm in somitogenesis: a player in the formation of the fibronectin matrix of presomitic mesoderm Development 134 :3155-3165

Pascoal, S., Carvalho, C., Rodriguez-León, J., Delphini, M.C., Duprez, D., Thorsteinsdóttir, S. and Palmeirim, I. (2007). A molecular clock operates during chick autopod proximal-distal outgrowth Journal of Molecular Biology 368 :303-309

Martins, G.G. and Kolega, J. (2006). Endothelial cell protrusion and migration in three-dimensional collagen matrices Cell Motility and the Cytoskeleton 63 :101-115

Bajanca, F., Luz M., Raymond, K., Martins, G.G., Sonnenberg, A., Tajbakhsh, S., Buckingham, M. and Thorsteinsdóttir, S. (2006). Integrin α6β1-laminin interactions regulate early myotome formation in the mouse embryo Development 133 :1635-1644

Cachaço, A.S., Pereira, C.S., Pardal, R.G, Bajanca, F. & Thorsteinsdóttir, S. (2005). The integrin repertoire on myogenic cells changes during the course of primary myogenesis in the mouse Developmental Dynamics 232 :1069-1078