PDGFR beta regulates craniofacial development through homodimers and functional heterodimers with PDGFR alpha

摘要

Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor a (PDGFR alpha) has well-documented functions in this process, the role of PDGFR beta in murine craniofacial development is not well established. We demonstrate that PDGFR alpha and PDGFR beta 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 PDGFR alpha and PDGFR beta 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.