Abstract
PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) αα and αβ dimers1,2. Here we show that Pdgfc−/− mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra−/− embryos. Pdgfc−/− Pdgfa−/− embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-α function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-α to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated.
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Acknowledgements
We thank P. Rowe and J. Rossant for reading the manuscript. This work was supported by grants from the National Cancer Institute of Canada Terry Fox Foundation (A.N.); the National Health and Medical Research Council of Australia (P.P.L.T.); and the National Institutes of Health, National Institute of Dental and Craniofacial Research (M.L.M. and L.L.F.). H.D. was supported by a fellowship from the Canadian Institute of Health Research and a developmental grant from the American Muscular Dystrophy Association. H.D. holds a Canada Research Chair. P.P.L.T. is a National Health and Medical Research Council Senior Principal Research Fellow and A.N. is a Senior Scientist of the Canadian Institute of Health Research.
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Supplementary Table 1
Incidence of fusion of palate shelves isolated from E13.5 pdgf-c mutant embryos in vitro. (PDF 2 kb)
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Ding, H., Wu, X., Boström, H. et al. A specific requirement for PDGF-C in palate formation and PDGFR-α signaling. Nat Genet 36, 1111–1116 (2004). https://doi.org/10.1038/ng1415
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DOI: https://doi.org/10.1038/ng1415
