Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning.
Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning.
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DOI：
10.1016/j.devcel.2009.11.013
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发表时间：
2010-01-19
影响因子：
11.8
通讯作者：
Logan, Malcolm P. O.
中科院分区：
文献类型：
--
作者：
Hasson, Peleg;DeLaurier, April;Bennett, Michael;Grigorieva, Elena;Naiche, L. A.;Papaioannou, Virginia E.;Mohun, Timothy J.;Logan, Malcolm P. O.
肌肉骨骼系统的正常运作需要骨骼、肌肉和肌腱的精确整合。复杂的形态发生事件确保这些元素以适当的3D配置连接在一起。然而，梳理出调节组织形态发生的机制一直很困难。我们发现，前肢Tbx5的缺失（或后肢Tbx4的缺失）特异性地影响肌肉和肌腱模式，而不破坏骨骼发育，从而表明不同的线索调节这些过程。我们确定肌肉结缔组织是这些转录因子的作用位点，并表明N-Cadherin和β-Catenin是肌肉结缔组织调节软组织形态发生的关键下游效应物。在人类中，TBX5突变导致Holt-Oram综合征，其特征是前肢肌肉骨骼缺陷。我们的结果表明，需要关注结缔组织，以了解影响软组织形成的疾病的病因学。
Proper functioning of the musculo-skeletal system requires the precise integration of bones, muscles and tendons. Complex morphogenetic events ensure that these elements are linked together in the appropriate 3D configuration. It has been difficult, however, to tease apart the mechanisms that regulate tissue morphogenesis. We find that deletion of Tbx5 in forelimb (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 β-Catenin are key downstream effectors acting in muscle connective tissue regulating soft-tissue morphogenesis. In humans, TBX5 mutations lead to Holt-Oram syndrome, which is characterised by forelimb musculo-skeletal defects. Our results suggest that a focus on connective tissue is required to understand the aetiology of diseases affecting soft tissue formation.
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影响因子：
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