Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration

Development. 2015 Jan 1;142(1):51-61. doi: 10.1242/dev.112557. Epub 2014 Dec 5.

Abstract

Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7(+)MyoD(-) cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7(+)MyoD(-) cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7(+)MyoD(+) myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7(+)MyoD(-) subpopulation, which contributes to myofiber maturation during muscle regeneration.

Keywords: Doublecortin; Myofiber maturation; Regeneration; Satellite cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotoxins / administration & dosage
  • Cell Differentiation*
  • Cell Movement
  • Cellular Microenvironment
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / metabolism*
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / physiology*
  • MyoD Protein / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Neuropeptides / deficiency
  • Neuropeptides / metabolism*
  • PAX7 Transcription Factor / metabolism
  • Regeneration / physiology*
  • Satellite Cells, Skeletal Muscle / cytology
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Cardiotoxins
  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • MyoD Protein
  • Neuropeptides
  • PAX7 Transcription Factor
  • Pax7 protein, mouse