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Nature Genetics
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A specific requirement for PDGF-C in palate formation and PDGFR-α signaling

Nature Geneticsvolume 36, pages1111–1116 (2004)Cite this article

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 thatPdgfc−/− 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 ofPdgfra−/− 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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Figure 1: Disruption ofPdgfc in mice.
Figure 2: Subepidermal blisters inPdgfc−/− embryos.
Figure 3: Cleft palate and spina bifida occulta.
Figure 4: Phenotypes of compound mutantPdgfc−/− Pdgfa−/− embryos at 10.5 d.p.c.
Figure 5: Phenotypes ofPdgfc−/− Pdgfa−/− embryos.

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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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Authors and Affiliations

  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

    Hao Ding, Xiaoli Wu & Andras Nagy

  2. Department of Medical Biochemistry, University of Goteborg, Sweden

    Hans Boström & Christer Betsholtz

  3. Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    Injune Kim & Gou Young Koh

  4. Embryology Unit, Children's Medical Research Institute and University of Sydney, Australia

    Nicole Wong, Bonny Tsoi, Meredith O'Rourke & Patrick P L Tam

  5. Division of Basic Sciences, Program in Developmental Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Philippe Soriano

  6. National Institute for Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland

    Thomas C Hart

  7. Center for Craniofacial and Dental Genetics, and Department of Human Genetics, University of Pittsburgh, Pennsylvania, USA

    Mary L Marazita

  8. Department of Medical Genetics, University of British Columbia, and B.C. Research Institute for Children's and Women's Health, Vancouver, Canada

    L L Field

  9. Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada

    Andras Nagy

Authors
  1. Hao Ding

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  6. Bonny Tsoi

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  7. Meredith O'Rourke

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  8. Gou Young Koh

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  9. Philippe Soriano

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  11. Thomas C Hart

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  14. Patrick P L Tam

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Corresponding author

Correspondence toAndras Nagy.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Incidence of fusion of palate shelves isolated from E13.5pdgf-c mutant embryosin 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 Genet36, 1111–1116 (2004). https://doi.org/10.1038/ng1415

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