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Letter
Nature Genetics  36, 1111 - 1116 (2004)
Published online: 7 September 2004; | doi:10.1038/ng1415

A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling

Hao Ding1, Xiaoli Wu1, Hans Boström2, Injune Kim3, Nicole Wong4, Bonny Tsoi4, Meredith O'Rourke4, Gou Young Koh3, Philippe Soriano5, Christer Betsholtz2, Thomas C Hart6, Mary L Marazita7, L L Field8, Patrick P L Tam4 & Andras Nagy1, 9

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

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

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

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

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

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

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

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

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

Correspondence should be addressed to Andras Nagy nagy@mshri.on.ca
PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta 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-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha 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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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