title: PDGFRβ regulates craniofacial development through homodimers and functional heterodimers with PDGFRα.
abstract: Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor α (PDGFRα) has well-documented functions in this process, the role of PDGFRβ in murine craniofacial development is not well established. We demonstrate that PDGFRα and PDGFRβ are coexpressed in the craniofacial mesenchyme of mid-gestation mouse embryos and that ablation of Pdgfrb in the neural crest lineage results in increased nasal septum width, delayed palatal shelf development, and subepidermal blebbing. Furthermore, we show that the two receptors genetically interact in this lineage, as double-homozygous mutant embryos exhibit an overt facial clefting phenotype more severe than that observed in either single-mutant embryo. We reveal a physical interaction between PDGFRα and PDGFRβ in the craniofacial mesenchyme and demonstrate that the receptors form functional heterodimers with distinct signaling properties. Our studies thus uncover a novel mode of signaling for the PDGF family during vertebrate development.
authors.affiliation: Department of Cell Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fantauzzo
authors.affiliation: Department of Cell Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Philippe
authors.identifier: 0000-0002-0427-926X
authors.initials: P
authors.lastname: Soriano
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics; D019281:Dimerization; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D009154:Mutation; D009432:Neural Crest / Q000196:embryology; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D012886:Skull / Q000196:embryology*
chemical_list: D016326:Extracellular Matrix Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: PDGFRα; PDGFRβ; craniofacial development; heterodimers; neural crest