title: Involvement of vessels and PDGFB in muscle splitting during chick limb development.
abstract: Muscle formation and vascular assembly during embryonic development are usually considered separately. In this paper, we investigate the relationship between the vasculature and muscles during limb bud development. We show that endothelial cells are detected in limb regions before muscle cells and can organize themselves in space in the absence of muscles. In chick limbs, endothelial cells are detected in the future zones of muscle cleavage, delineating the cleavage pattern of muscle masses. We therefore perturbed vascular assembly in chick limbs by overexpressing VEGFA and demonstrated that ectopic blood vessels inhibit muscle formation, while promoting connective tissue. Conversely, local inhibition of vessel formation using a soluble form of VEGFR1 leads to muscle fusion. The endogenous location of endothelial cells in the future muscle cleavage zones and the inverse correlation between blood vessels and muscle suggests that vessels are involved in the muscle splitting process. We also identify the secreted factor PDGFB (expressed in endothelial cells) as a putative molecular candidate mediating the muscle-inhibiting and connective tissue-promoting functions of blood vessels. Finally, we propose that PDGFB promotes the production of extracellular matrix and attracts connective tissue cells to the future splitting site, allowing separation of the muscle masses during the splitting process.
authors.affiliation: Biologie du Développement, CNRS, UMR 7622, Université P. et M. Curie, 9 Quai Saint-Bernard, Bât. C, 6 E, Case 24, 75252 Paris Cedex 05, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Tozer
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Bonnin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Relaix
authors.forename: Sandrine
authors.initials: S
authors.lastname: Di Savino
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Villalba
authors.forename: Pascal
authors.initials: P
authors.lastname: Coumailleau
authors.forename: Delphine
authors.initials: D
authors.lastname: Duprez
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D019521:Body Patterning; D002642:Chick Embryo; D003238:Connective Tissue / Q000196:embryology; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000196:embryology*; D005109:Extracellular Matrix / Q000502:physiology; D005121:Extremities / Q000098:blood supply / Q000196:embryology* / Q000502:physiology; D009024:Morphogenesis; D018482:Muscle, Skeletal / Q000098:blood supply / Q000196:embryology* / Q000502:physiology; D017570:MyoD Protein / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D017570:MyoD Protein; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1