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A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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2004 (English)In: Nat Genet, ISSN 1061-4036, Vol. 36, no 10, 1111-6 p.Article in journal (Refereed) Published
Abstract [en]

PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. 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.

Place, publisher, year, edition, pages
2004. Vol. 36, no 10, 1111-6 p.
Keyword [en]
Abnormalities; Multiple/embryology/genetics, Animals, Animals; Newborn, Cleft Palate/embryology/genetics, Gene Expression Regulation; Developmental, Mice, Mice; Knockout, Palate/*embryology, Phenotype, Platelet-Derived Growth Factor/deficiency/genetics/*physiology, Receptor; Platelet-Derived Growth Factor alpha/deficiency/genetics/*physiology, Research Support; Non-U.S. Gov't, Research Support; U.S. Gov't; P.H.S., Signal Transduction, Spina Bifida Occulta/embryology/genetics
URN: urn:nbn:se:uu:diva-73148PubMedID: 15361870OAI: oai:DiVA.org:uu-73148DiVA: diva2:101059
Available from: 2005-06-01 Created: 2005-06-01 Last updated: 2011-01-12

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Boström, Hans
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