EZH2 modulates retinoic acid signaling to ensure myotube formation during development. Issue 13 (27th March 2022)

• Record Type: Journal Article
• Authors: Thulabandu, Venkata; Ferguson, James W.; Phung, Melissa; Atit, Radhika P.
• Is Part Of: FEBS letters. Volume 596:Issue 13(2022)
• Page Start: 1672
• Page End: 1685
• Publication Date: 2022-03-27
• Subjects: muscle development -- muscle differentiation program -- myotube formation -- polycomb repressive complex2 -- retinoic acid signaling; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14334
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Sequential differentiation of presomitic progenitors into myocytes and subsequently into myotubes and myofibers is essential for the myogenic differentiation program (MDP) crucial for muscle development. Signaling factors involved in MDP are polycomb repressive complex 2 (PRC2) targets in various developmental contexts. PRC2 is active in the developing myotomes during MDP, but how it regulates MDP is unclear. Here, we found that myocyte differentiation to myotubes requires Enhancer of Zeste 2 (EZH2), the catalytic component of PRC2. We observed elevated retinoic acid (RA) signaling in the prospective myocytes in the Ezh2 mutants (E8.5‐Mus Ezh2 ), and its inhibition can partially rescue the myocyte differentiation defect. Together, our data demonstrate a new role for PRC2–EZH2 during myocyte differentiation into myotubes by modulating RA signaling. Abstract : Sequential differentiation of presomitic progenitors to mature myofibres is essential for embryonic muscle development. In the absence of mesenchymal Ezh2, the catalytic component of polycomb repressive complex 2, the differentiation of myocytes to myotubes is halted while retinoic acid signaling is elevated. We rescued myocyte differentiation in the Ezh2 mutants with a small molecule inhibitor of retinoic acid signaling.