Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons

Nicholas D. Murchison, Brian A. Price, David A. Conner, Douglas R. Keene, Eric N. Olson, Clifford J. Tabin, Ronen Schweitzer

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

The scleraxis (ScK) gene, encoding a bHLH transcription factor, is expressed in the progenitors and cells of all tendon tissues. To determine Scx function, we produced a mutant null allele. Scx-/- mice were viable, but showed severe tendon defects, which manifested in a drastically limited use of all paws and back muscles and a complete inability to move the tail. Interestingly, although the differentiation of all force-transmitting and intermuscular tendons was disrupted, other categories of tendons, the function of which is mainly to anchor muscles to the skeleton, were less affected and remained functional, enabling the viability of SCx-/- mutants. The force-transmitting tendons of the limbs and tail varied in the severity to which they were affected, ranging from dramatic failure of progenitor differentiation resulting in the loss of segments or complete tendons, to the formation of small and poorly organized tendons. Tendon progenitors appeared normal in Scx-/- embryos and a phenotype resulting from a failure in the condensation of tendon progenitors to give rise to distinct tendons was first detected at embryonic day (E)13.5. In the tendons that persisted in Scx-/- mutants, we found a reduced and less organized tendon matrix and disorganization at the cellular level that led to intermixing of tenocytes and endotenon cells. The phenotype of Scx-/- mutants emphasizes the diversity of tendon tissues and represents the first molecular insight into the important process of tendon differentiation.

Original languageEnglish (US)
Pages (from-to)2697-2708
Number of pages12
JournalDevelopment
Volume134
Issue number14
DOIs
StatePublished - Jul 1 2007

Keywords

  • Connective tissue
  • Mouse mutant
  • Scleraxis
  • Tendon

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons'. Together they form a unique fingerprint.

  • Cite this

    Murchison, N. D., Price, B. A., Conner, D. A., Keene, D. R., Olson, E. N., Tabin, C. J., & Schweitzer, R. (2007). Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development, 134(14), 2697-2708. https://doi.org/10.1242/dev.001933