Pax3:Foxc2 Reciprocal Repression in the Somite Modulates Muscular versus Vascular Cell Fate Choice in Multipotent Progenitors

Mounia Lagha, Silvia Brunelli, Graziella Messina, Ana Cumano, Tsutomu Kume, Frédéric Relaix, Margaret E. Buckingham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Maintenance of multipotency and how cells exit this state to adopt a specific fate are central questions in stem cell biology. During vertebrate development, multipotent cells of the dorsal somite, the dermomyotome, give rise to different lineages such as vascular smooth and skeletal muscle, regulated by the transcription factors Foxc2 and Pax3, respectively. Here we show reciprocal inhibition between Pax3 and Foxc2 in the mouse embryo. Using both genetic approaches and manipulation of external signals in somite explants, we demonstrate that the Pax3:Foxc2 ratio modulates myogenic versus vascular cell fates. This provides insight into how cell fate choices are orchestrated by these lineage genes in the dermomyotome.

Original languageEnglish (US)
Pages (from-to)892-899
Number of pages8
JournalDevelopmental Cell
Volume17
Issue number6
DOIs
StatePublished - Dec 15 2009

Funding

We thank C. Bodin for excellent technical help and J.-F. Le Garrec for theoretical insights. We thank D. Rocancourt for artwork, A. Mayeuf for help with immunohistochemistry ( Figure S3 ), and G. Pallafacchina for advice on qPCR. We are grateful to E. Perret and to A. Danckaert for their assistance with image acquisition and quantification. All images were assembled in Adobe Photoshop. M.B.'s laboratory is financed by the Pasteur Institute and CNRS, with grants from the AFM and the EU-MYORES (CT04-511978), EuroSyStem (F407-200720), and OptiStem (F408-223098), which also finances S.B. and G.M. M.L. had fellowships from the AFM and OptiStem. This work was also supported by a Canceropole IDF (FNS20041) grant to F.R.

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • Cell Biology
  • Developmental Biology

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