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Publication : Involvement of vessels and PDGFB in muscle splitting during chick limb development.

First Author  Tozer S Year  2007
Journal  Development Volume  134
Issue  14 Pages  2579-91
PubMed ID  17553906 Mgi Jnum  J:122753
Mgi Id  MGI:3715401 Doi  10.1242/dev.02867
Citation  Tozer S, et al. (2007) Involvement of vessels and PDGFB in muscle splitting during chick limb development. Development 134(14):2579-91
abstractText  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.
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