Résumé :
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Communication n° 655. Development and function of muscle are controlled by a large number of soluble factors and require multiple interactions with the components of the extracellular matrix, which composition and functional properties differs depending on muscle type. Collagen XV is a component of basement membranes and is expressed mainly in heart and skeletal muscles. The lack of collagen XV in mice results in a mild skeletal myopathy suggesting a role of this collagen in muscle morphogenesis and function. The goal of the present project is to study the in vivo function of collagen XV during the development of skeletal muscles. The originality of our approach is to use zebrafish as a model in which 63 mutants exhibit a reduction of the striation of somitic muscles. Thus, the interplay between collagen and the factors involved in myogenic regulation could be analysed. In a preliminary study, we have determined the complete primary sequence of zebrafish collagen XV and shown a restricted expression in the notochord during the segmentation period. We have started a study of collagen XV function using a double approach combining a knock-down analysis using the morpholino antisens technology and an in vivo overexpression of restin, a C-terminal fragment of collagen XV known to inhibit angiogenesis. Morpholino injected embryos revealed defects in motility and muscle differentiation as shown by video-tape and cytological analysis. Presently, the consequence of knock-down and overexpression of collagen XV in muscle specification and motorneuron differentiation in which the notochord is implicated, will be determined using a panel of methodologies in which we have a good expertise, such as immunolabelling using specific antibodies against both the trunk muscle type and somitic motorneurons. An important part of this project will be the analysis of the influence of collagen XV on the expression of multiple myogenic regulator such as MyoD and Myf5.
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