Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation

Brian A. Pryce, Spencer S. Watson, Nicholas D. Murchison, Julia Staverosky, Nicole Dünker, Ronen Schweitzer

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

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 TGFβ signaling plays a major role in the formation of these tissues. TGFβ signaling is a potent inducer of the tendon progenitor (TNP) marker scleraxis both in organ culture and in cultured cells, and disruption of TGFβ signaling in Tgfb2-/-;Tgfb3-/- double mutant embryos or through inactivation of the type II TGFβ receptor (TGFBR2; also known as TβRII) 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. TGFβ 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 muskoskeletal system.

Original languageEnglish (US)
Pages (from-to)1351-1361
Number of pages11
JournalDevelopment
Volume136
Issue number8
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

Fingerprint

Tendons
Maintenance
Cartilage
Ligaments
Muscles
Embryonic Structures
Bone and Bones
Musculoskeletal System
Organ Culture Techniques
Muscle Cells
Cultured Cells
Extremities
Head
Phenotype

Keywords

  • Connective tissue
  • Ligaments
  • Mouse
  • Tendons
  • TGFΒ

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Pryce, B. A., Watson, S. S., Murchison, N. D., Staverosky, J., Dünker, N., & Schweitzer, R. (2009). Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation. Development, 136(8), 1351-1361. https://doi.org/10.1242/dev.027342

Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation. / Pryce, Brian A.; Watson, Spencer S.; Murchison, Nicholas D.; Staverosky, Julia; Dünker, Nicole; Schweitzer, Ronen.

In: Development, Vol. 136, No. 8, 15.04.2009, p. 1351-1361.

Research output: Contribution to journalArticle

Pryce, BA, Watson, SS, Murchison, ND, Staverosky, J, Dünker, N & Schweitzer, R 2009, 'Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation', Development, vol. 136, no. 8, pp. 1351-1361. https://doi.org/10.1242/dev.027342
Pryce BA, Watson SS, Murchison ND, Staverosky J, Dünker N, Schweitzer R. Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation. Development. 2009 Apr 15;136(8):1351-1361. https://doi.org/10.1242/dev.027342
Pryce, Brian A. ; Watson, Spencer S. ; Murchison, Nicholas D. ; Staverosky, Julia ; Dünker, Nicole ; Schweitzer, Ronen. / Recruitment and maintenance of tendon progenitors by TGFΒ signaling are essential for tendon formation. In: Development. 2009 ; Vol. 136, No. 8. pp. 1351-1361.
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