Extracellular Matrix

Research Interests

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.

Group Members

Research Project

Integrating signals in morphogenesis: The case of somitogenesis in the chick embryo

Somites are blocks of cells that form in a coordinated fashion along the anterior posterior axis of vertebrate embryos. Somite formation involves the separation and epithelialisation of a group of cells in the anterior part of the presomitic mesoderm. We are using high resolution 3D imaging/analysis techniques over time to characterise the locomotive, cytoskeletal and adhesive properties of chick PSM cells and the organisation of their surrounding ECM. We also experimentally manipulate the availability of ECM molecules and paracrine factors and determine the effect on PSM cell behaviour.

Funding

POCTI/BIA-BCM/59201/2004
Sólveig Thorsteinsdóttir

Collaborators

Instituto de Investigação em Ciências da Vida e Saúde/ Escola de Ciências da Saúde, Universidade do Minho, Portugal
We are collaborating with Isabel Palmeirim and her group at the University of Minho and with Leonor Saúde and António Jacinto at the IMM.

Network of Excellence “Cells into Organs” (FP6/EU)
We are collaborating with several groups within this Network
(www.cellsintoorgans.net)

Research Project

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

Collaborators

University of Otago, Dunedin, New Zealand
We are collaborating with Marilyn J. Duxson

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

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

Network of Excellence “Cells into Organs” (FP6/EU)
We are collaborating with several groups within this Network
(www.cellsintoorgans.net)

Publications

Martins, G.G., Rifes, P., Amândio, R., Campinho, P., Palmeirim, I. & Thorsteinsdóttir, S. (2007). 3D visualization and analysis of cell-matrix transformations in whole-mount and live embryos using confocal and multi-photon microscopy. pp. 426-433. In A. Méndez-Vilas, J. Díaz (Eds.) . (ISBN-13:978-84-611-9419-3). Modern Research and Educational to Topics in Microscopy Microscopy Series nº 3, Vol. 1 :Formatex, Badajoz, Spain

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

Chuva de Sousa Lopes, S.M., Mummery, C.L. and Thorsteinsdóttir, S. (2004). Implantation and placentation. In "Cell Signalling and growth factors in development: from molecules to organogenesis" (Unsicker K. and Krieglstein K., eds.), Wiley-VCH Publishers Weinheim (ISBN 3-527-31034-7) :73-105

Bajanca, F., Luz, M., Duxson, M.J. and Thorsteinsdóttir, S. (2004). Integrins in the mouse myotome: developmental changes and differences between the epaxial and hypaxial lineage. Developmental Dynamics 231 :402-415

Cachaço, A.S., Chuva de Sousa Lopes, S.M., Kuikman, I., Bajanca, F., Abe, K., Baudoin, C., Sonnenberg, A., Mummery, C.L. and Thorsteinsdóttir, S. (2003). Knock-in of integrin β1D affects primary but not secondary myogenesis in mice. Development 130 :1659-1671

Bajanca, F. and Thorsteinsdóttir, S. (2002). Integrin expression patterns during early limb muscle development in the mouse. Mechanisms of Development 119(1) :S131-S134

Thorsteinsdóttir, S., Roelen, B.A.J., Goumans, M.-J., Ward-van Oostwaard, D., Gaspar, A.C. and Mummery, C.L. (1999). Expression of the a6A integrin splice variant in developing mouse embryonic stem cell aggregates and correlation with cardiac muscle differentiation. Differentiation 64 :173-184.

van der Neut, R., Cachaço, A.S., Thorsteinsdóttir, S., Janssen, H., Prins, D., Bulthuis, J., van der Valk, M., Calafat, J. and Sonnenberg, A (1999). Rescue of epithelial phenotype in integrin ß4 null mice by a keratin-5 promoter driven human integrin ß4 transgene Journal of Cell Scence 112: 112 :3911-3922

Venters, S.A., Thorsteinsdóttir, S. and Duxson, M.J (1999). Early development of the myotome in the mouse. Developmental Dynamics 216 :219-232

van der Flier, A., Gaspar, A.C., Thorsteinsdóttir, S., Baudoin, C., Groeneveld, E., Mummery, C.L. and Sonnenberg, A. (1997). Spatial and temporal expression of the ß1D integrin during mouse development Developmental Dynamics 210 :472-486

Thorsteinsdóttir, S., Roelen, B.A.J., Freund, E., Gaspar, A.C., Sonnenberg, A. e Mummery, C.L. (1995). Expression patterns of laminin receptor splice variants a6Aß1 and a6Bß1 suggests different roles in mouse development Developmental Dynamics 204 :240-258

Hierck, B., Thorsteinsdóttir, S., Niessen, C., Freund, E., Iperen, L., Feyen, A., Hogervorst, F., Poelmann, R., Mummery, C.L. and Sonnenberg, A. (1993). Variants of the a6ß1 laminin receptor in early murine development: distribution, molecular cloning and chromosomal localization of the mouse integrin a6 subunit. Cell Adhesion and Communication 1 :33-53

Thorsteinsdóttir, S. (1992). Basement membrane and fibronectin matrix are distinct entities in the developing mouse blastocyst. Anatomical Record 232 :141-149

Cidadão, A.J., Thorsteinsdóttir, S. and David-Ferreira, J.F. (1990). Immunocytochemical study of tissue distribution and hormonal control of chondroitin-, dermatan- and keratan sulfates from rodent uterus. European Journal of Cell Biology 52 :105-116

Thorsteinsdóttir, S. (1988). Compaction: the first differentiation event in mammalian embryogenesis. Revista Medicina 1 :23-29

Cidadão A.J., Thorsteinsdóttir, S. and David-Ferreira, J.F. (1988). Immunocytochemical study of fibronectin distribution in tissues: A re-evaluation of fibronectin-collagen interactions. Journal of Histochemistry and Cytochemistry 36 :639-648

Frost, S.K., Robinson, S.J., Carson, M.K., Thorsteinsdóttir, S. and Giesler, J. (1987). Effects of exogenous guanosine on chromatophore differentiation in the axolotl. Pigment Cell Research 1 :37-43

Frost, S.K., Borchert, M.E. and Thorsteinsdóttir, S. (1986). A rapid and sensitive TLC assay procedure for measuring xanthine dehydrogenase activity from tissue extracts. Journal of Chromatography 382 :314-320

Thorsteinsdóttir, S. and Frost, S.K. (1986). Pigment cell differentiation: The relationship between pterin content, allopurinol treatment and the melanoid gene in the axolotl. Cell Differentiation 19 :161-172