Recruitment and maintenance of tendon progenitors by TGFβ signaling are essential for tendon formation
Recruitment and maintenance of tendon progenitors by TGFβ signaling are essential for tendon formation
复制标题
DOI：
10.1242/dev.027342
复制
发表时间：
2009-04-15
期刊：
影响因子：
4.6
通讯作者：
Schweitzer, Ronen
中科院分区：
文献类型：
--
作者：
Pryce, Brian A.;Watson, Spencer S.;Schweitzer, Ronen
肌腱和韧带介导肌肉与骨以及骨与骨的附着，以在肌肉骨骼系统中提供连接性和结构完整性。我们发现TGF β信号在这些组织的形成中起着重要作用。TGF α信号传导是器官培养物和培养细胞中腱祖细胞（TNP）标记物巩膜轴的有效诱导物，并且Tgfb 2（-/-）; Tgfb 3（-/-）双突变胚胎中TGF β信号传导的破坏或通过II型TGF β受体（TGFBR 2;也称为T β RII）的失活导致肢体、躯干、尾部和头部中的大多数腱和韧带的损失。在突变胚胎中，表达巩膜的TNP的诱导不受影响，并且肌腱表型首先在E12.5显现，E12.5是一个发育阶段，其中TNP位于分化的肌肉和软骨之间，并且其中Tgfb 2或Tgfb 3在TNP和分化的肌肉和软骨中表达。因此，TGF α信号传导对于TNP的维持是必不可少的，并且我们提出，它还通过分化肌肉和软骨来介导新肌腱细胞的招募，以建立肌腱原基与其各自的肌肉骨骼对应物之间的连接，从而形成相互关联且功能整合的肌肉骨骼系统。
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 TGF beta signaling plays a major role in the formation of these tissues. TGF alpha signaling is a potent inducer of the tendon progenitor (TNP) marker scleraxis both in organ culture and in cultured cells, and disruption of TGF beta signaling in Tgfb2(-/-); Tgfb3(-/-) double mutant embryos or through inactivation of the type II TGF beta receptor (TGFBR2; also known as T beta RII) 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. TGF alpha 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.