MRC National Institute for Medical Research, London
Science for Health
Limb morphogenesis
25 January 2010
Proper functioning of the musculoskeletal system requires the precise integration of bones, muscles and tendons. Complex morphogenetic events ensure that these elements are linked together in the appropriate three-dimensional configuration. It has proven difficult to tease apart the mechanisms that regulate tissue morphogenesis.
Malcolm Logan's group in NIMR's Division of Developmental Biology has analysed the mechanisms regulating limb muscle and tendon morphogenesis in the developing embryo and shown how these events are regulated at the tissue and molecular level. In this work his research group has demonstrated the role of connective tissue in these morphogenetic processes and provided the basis for understanding of how these patterning events are regulated at the tissue and molecular level. They identifed the genes Tbx5 and Tbx4 in the forelimb and hindlimb, respectively, and two downstream targets, b-Catenin and N-Cadherin, as regulators of muscle connective tissue organisation.
Mispatterning of tendons does not prevent their interactions with muscles and skeleton.
OPT analysis of whole-mount immunohistochemistry of (A and C) E15.5 control and (B and D) Tbx5-deleted autopods, of which TM was administered at E9.5, showing mispatterning of muscles (red) and tendons (green).
Our data suggest that the core mechanisms regulating the size, shape and insertions sites of limb muscles and tendons are shared by the head and skeletal muscles and that a focus on connective tissue will be required to understand the aetiology of human congenital muscle and tendon dysplasia.
Malcolm Logan
Original article
The research findings are published in full in:
Peleg Hasson, April DeLaurier, Michael Bennett, Elena Grigorieva, L.A. Naiche, Virginia E. Papaioannou, Timothy J. Mohun, Malcolm P.O. Logan. (2010)
Tbx4 and Tbx5 acting in connective tissue are required for limb muscle and tendon patterning
Developmental Cell, 18(1): 148-156. Publisher abstract
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