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Cellular Interactions with Extracellular Matrix During Development and in Muscle Disease

<p>The formation and maintenance of tissues in multicellular animals are crucially dependent on cellular interactions with the extracellular matrix (ECM). Two different studies on such interactions are presented herein.</p><p>Studies on expression of laminins in normal and dystrophic skeletal muscle, clarified a much debated issue regarding discrepancies seen for laminin α1-chain expression between human and mouse tissues. Lack of laminin α1-chain expression was verified in both mouse and human skeletal muscle. Furthermore, the earlier discrepancies seen for laminin α1-chain expression was explained by showing that an antibody-reagent, commonly used in human studies, recognised the laminin α5-chain rather than the laminin α1-chain</p><p>The integrin α11-chain (forming α11β1 integrin) is the latest addition to the integrin receptor family, and belongs to the I domain-containing group of integrin α-chains. Previous studies had shown that α11β1 is a collagen receptor. In the present study, the <i>in vitro</i> and <i>in vivo</i> functions of the α11-chain were further characterised. Distribution studies on embryonic human and mouse tissues showed that the α11-chain was expressed on mesenchymal cells in the developing tendon, perichondrium, intervertebral disc, and cornea. The interactions of α11β1 integrin with collagen type I and IV were studied <i>in vitro</i>. The α11β1 bound to these collagens in a manner similar to integrin α2β1 (with collagen type I being the preferred ligand for α11β1). Furthermore, α11β1 was shown to mediate migration on collagen type I coated surfaces, and to mediate contraction of collagen type I gels. The <i>in vivo</i> functions of the α11-chain were investigated by the generation of integrin α11-chain null-mice, using gene targeted disruption of the itga11 in embryonic stem cells. Two independent lines of mice lacking α11 protein were generated. Phenotypic analysis of these mice indicated a role for α11β1 in the formation of the musculoskeletal system.</p>

Identiferoai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-2007
Date January 2002
CreatorsTiger, Carl-Fredrik
PublisherUppsala University, Department of Cell and Molecular Biology, Uppsala : Acta Universitatis Upsaliensis
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeDoctoral thesis, comprehensive summary, text
RelationComprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1104-232X ; 720

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