title: Endothelial cell specification in the somite is compromised in Pax3-positive progenitors of Foxc1/2 conditional mutants, with loss of forelimb myogenesis.
abstract: Pax3 and Foxc2 have been shown genetically to mutually repress each other in the mouse somite. Perturbation of this balance in multipotent cells of the dermomyotome influences cell fate; upregulation of Foxc2 favours a vascular fate, whereas higher levels of Pax3 lead to myogenesis. Foxc1 has overlapping functions with Foxc2. In Foxc1/2 double-mutant embryos, somitogenesis is severely affected, precluding analysis of somite derivatives. We have adopted a conditional approach whereby mutations in Foxc1 and Foxc2 genes were targeted to Pax3-expressing cells. Inclusion of a conditional reporter allele in the crosses made it possible to follow cells that had expressed Pax3. At the forelimb level, endothelial and myogenic cells migrate from adjacent somites into the limb bud. This population of endothelial cells is compromised in the double mutant, whereas excessive production of myogenic cells is observed in the trunk. However, strikingly, myogenic progenitors fail to enter the limbs, leading to the absence of skeletal muscle. Pax3-positive migratory myogenic progenitors, marked by expression of Lbx1, are specified in the somite at forelimb level, but endothelial progenitors are absent. The myogenic progenitors do not die, but differentiate prematurely adjacent to the somite. We conclude that the small proportion of somite-derived endothelial cells in the limb is required for the migration of myogenic limb progenitors.
authors.affiliation: CNRS UMR 3738, Department of Developmental and Stem Cell Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Mayeuf-Louchart
authors.affiliation: CNRS UMR 3738, Department of Developmental and Stem Cell Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Montarras
authors.affiliation: CNRS UMR 3738, Department of Developmental and Stem Cell Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bodin
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kume
authors.affiliation: CNRS UMR 3738, Department of Developmental and Stem Cell Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France.
authors.forename: Stéphane D
authors.initials: SD
authors.lastname: Vincent
authors.affiliation: CNRS UMR 3738, Department of Developmental and Stem Cell Biology, Institut Pasteur, 28 Rue du Dr Roux, Paris 75015, France margaret.buckingham@pasteur.fr.
authors.forename: Margaret
authors.initials: M
authors.lastname: Buckingham
mesh_terms: D000818:Animals; D002465:Cell Movement; D002469:Cell Separation; D003433:Crosses, Genetic; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005552:Forelimb / Q000196:embryology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D017403:In Situ Hybridization; D018878:Limb Buds / Q000196:embryology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019170:Somites / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C082078:mesenchyme fork head 1 protein; C068686:Pax3 protein, mouse
keywords: Forelimb bud; Foxc1; Foxc2; Mouse embryo; Myogenic cells; Pax3; Somite-derived endothelial cells
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