A requirement of polo-like Kinase 1 in murine embryonic myogenesis and adult muscle regeneration

Zhihao Jia, Yaohui Nie, Feng Yue, Yifan Kong, Lijie Gu, Timothy P. Gavin, Xiaoqi Liu, Shihuan Kuang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Muscle development and regeneration require delicate cell cycle regulation of embryonic myoblasts and adult muscle satellite cells (MuSCs). Through analysis of the Polo-like kinase (Plk) family cell-cycle regulators in mice, we show that Plk1’s expression closely mirrors myoblast dynamics during embryonic and postnatal myogenesis. Cell-specific deletion of Plk1 in embryonic myoblasts leads to depletion of myoblasts, developmental failure and prenatal lethality. Postnatal deletion of Plk1 in MuSCs does not perturb their quiescence but depletes activated MuSCs as they enter the cell cycle, leading to regenerative failure. The Plk1-null MuSCs are arrested at the M-phase, accumulate DNA damage, and apoptose. Mechanistically, Plk1 deletion upregulates p53, and inhibition of p53 promotes survival of the Plk1-null myoblasts. Pharmacological inhibition of Plk1 similarly inhibits proliferation but promotes differentiation of myoblasts in vitro, and blocks muscle regeneration in vivo. These results reveal for the first time an indispensable role of Plk1 in developmental and regenerative myogenesis.

Original languageEnglish
Article numbere47097
JournaleLife
Volume8
DOIs
StatePublished - Aug 2019

Bibliographical note

Publisher Copyright:
© Jia et al.

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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