Ezh2 Is Essential for Patterning of Multiple Musculoskeletal Tissues but Dispensable for Tendon Differentiation

Deepanwita Pal, Scott M. Riester, Bashar Hasan, Sara F. Tufa, Amel Dudakovic, Douglas R. Keene, Andre J van Wijnen, Ronen Schweitzer

Research output: Contribution to journalArticlepeer-review

Abstract

An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton, and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting Ezh2 through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by Ezh2 for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of Ezh2 in the tendon cells did not disrupt overall tendon structure or collagen organization suggesting that tendon differentiation and maturation are independent of Ezh2 signaling.

Original languageEnglish (US)
Pages (from-to)601-609
Number of pages9
JournalStem Cells and Development
Volume30
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • epigenetics
  • Ezh2
  • musculoskeletal
  • patterning
  • tendon

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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