Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning

Joana Esteves de Lima, Cédrine Blavet, Marie-Ange Bonnin, Estelle Hirsinger, Glenda Comai, Laurent Yvernogeau, Marie-Claire Delfini, Léa Bellenger, Sébastien Mella, Sonya Nassari, Catherine Robin, Ronen Schweitzer, Claire Fournier-Thibault, Thierry Jaffredo, Shahragim Tajbakhsh, Frédéric Relaix, Delphine Duprez

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction. Analysis of single-cell RNA-sequencing data from whole limbs at successive developmental stages identifies a population displaying a dual muscle and connective tissue signature. BMP signalling is active in this dual population and at the tendon/muscle interface. In vivo and in vitro gain- and loss-of-function experiments show that BMP signalling regulates a fibroblast-to-myoblast conversion. These results suggest a scenario in which BMP signalling converts a subset of lateral plate mesoderm-derived cells to a myogenic fate in order to create a boundary of fibroblast-derived myonuclei at the myotendinous junction that controls limb muscle patterning.

Original languageEnglish
Pages (from-to)3851
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 22 Jun 2021

Keywords

  • Animals
  • Body Patterning/genetics
  • Cell Lineage/genetics
  • Cells, Cultured
  • Chick Embryo
  • Extremities/embryology
  • Fibroblasts/cytology
  • Gene Expression Regulation, Developmental
  • Mesoderm/cytology
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Muscle Development/genetics
  • Muscle, Skeletal/cytology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Somites/cytology

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