Pryce Brian A, Watson Spencer S, Murchison Nicholas D, Staverosky Julia A, Dünker Nicole, Schweitzer Ronen
Shriners Hospital for Children, Research Division, Portland, OR 97239, USA.
Development. 2009 Apr;136(8):1351-61. doi: 10.1242/dev.027342.
Tendons and ligaments mediate the attachment of muscle to bone and of bone to bone to provide connectivity and structural integrity in the musculoskeletal system. We show that TGFbeta signaling plays a major role in the formation of these tissues. TGFbeta signaling is a potent inducer of the tendon progenitor (TNP) marker scleraxis both in organ culture and in cultured cells, and disruption of TGFbeta signaling in Tgfb2(-/-);Tgfb3(-/-) double mutant embryos or through inactivation of the type II TGFbeta receptor (TGFBR2; also known as TbetaRII) results in the loss of most tendons and ligaments in the limbs, trunk, tail and head. The induction of scleraxis-expressing TNPs is not affected in mutant embryos and the tendon phenotype is first manifested at E12.5, a developmental stage in which TNPs are positioned between the differentiating muscles and cartilage, and in which Tgfb2 or Tgfb3 is expressed both in TNPs and in the differentiating muscles and cartilage. TGFbeta signaling is thus essential for maintenance of TNPs, and we propose that it also mediates the recruitment of new tendon cells by differentiating muscles and cartilage to establish the connections between tendon primordia and their respective musculoskeletal counterparts, leading to the formation of an interconnected and functionally integrated musculoskeletal system.
肌腱和韧带介导肌肉与骨骼以及骨骼与骨骼之间的附着，以在肌肉骨骼系统中提供连接性和结构完整性。我们发现转化生长因子β（TGFβ）信号通路在这些组织的形成中起主要作用。在器官培养和培养细胞中，TGFβ信号通路都是肌腱祖细胞（TNP）标志物硬骨素的有效诱导剂，并且在Tgfb2（-/-）；Tgfb3（-/-）双突变胚胎中或通过II型TGFβ受体（TGFBR2；也称为TbetaRII）失活来破坏TGFβ信号通路，会导致四肢、躯干、尾巴和头部的大多数肌腱和韧带缺失。在突变胚胎中，表达硬骨素的TNP的诱导不受影响，并且肌腱表型首先在E12.5出现，这是一个发育阶段，此时TNP位于分化的肌肉和软骨之间，并且Tgfb2或Tgfb3在TNP以及分化的肌肉和软骨中均有表达。因此，TGFβ信号通路对于TNP的维持至关重要，并且我们提出它还通过分化的肌肉和软骨介导新肌腱细胞的募集，以建立肌腱原基与其各自的肌肉骨骼对应物之间的连接，从而导致形成相互连接且功能整合的肌肉骨骼系统。
