期刊
DEVELOPMENTAL CELL
卷 18, 期 1, 页码 148-156出版社
CELL PRESS
DOI: 10.1016/j.devcel.2009.11.013
关键词
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资金
- European Molecular Biology Organisation (EMBO) Long-term Fellowship
- Medical Research Council (UK)
- National Institutes of Health [HD033082]
- Mandl Connective Tissue Fellowship
- MRC [MC_U117560477, MC_U117562103] Funding Source: UKRI
- Medical Research Council [MC_U117560477, MC_U117562103] Funding Source: researchfish
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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