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Publication : Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning.

First Author  Hasson P Year  2010
Journal  Dev Cell Volume  18
Issue  1 Pages  148-56
PubMed ID  20152185 Mgi Jnum  J:157917
Mgi Id  MGI:4437355 Doi  10.1016/j.devcel.2009.11.013
Citation  Hasson P, et al. (2010) Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning. Dev Cell 18(1):148-56
abstractText  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 been difficult, however, to tease apart the mechanisms that regulate tissue morphogenesis. We find that deletion of Tbx5 in forelimbs (or Tbx4 in hindlimbs) specifically affects muscle and tendon patterning without disrupting skeletal development, thus suggesting that distinct cues regulate these processes. We identify muscle connective tissue as the site of action of these transcription factors and show that N-Cadherin and beta-Catenin are key downstream effectors acting in muscle connective tissue and regulating soft-tissue morphogenesis. In humans, TBX5 mutations lead to Holt-Oram syndrome, which is characterized by forelimb musculoskeletal defects. Our results suggest that a focus on connective tissue is required to understand the etiology of diseases affecting soft tissue formation.
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