PDGF‐B: The missing piece in the mosaic of PDGF family role in craniofacial development

Background The platelet‐derived growth factor (PDGF) family consists of four ligands (PDGF‐A, PDGF‐B, PDGF‐C, PDGF‐D) and two tyrosine kinase receptors (PDGFR‐α and PDGFR‐β). In vertebrates, PDGF signaling influences cell proliferation, migration, and matrix deposition, and its up‐regulation is implicated in cancer progression. Despite this evidence, the role of each family member during embryogenesis is still incomplete and partially controversial. In particular, study of the role of pdgf signaling during craniofacial development has been focused on pdgf‐a, while the role of pdgf‐b is almost unknown due to the lethal phenotypes of pdgf‐b‐null mice. Results By using a pdgf‐b splice‐blocking morpholino approach, we highlighted impairment of neural crest cell (NCC) migration in Xenopus laevis morphants, leading to alteration of NCC derivatives formation, such as cranial nerves and cartilages. We also uncovered a possible link between pdgf‐b and the expression of cadherin superfamily members cdh6 and cdh11, which mediate cell‐cell adhesion promoting NCC migration. Conclusions Our results suggested that pdgf‐b signaling is involved in cranial NCC migration and it is required for proper formation of craniofacial NCC derivatives. Taken together, these data unveiled a new role for pdgf‐b during vertebrate development, contributing to complete the picture of pdgf signaling role in craniofacial development. Key Findings Pdgf‐b is required for craniofacial development in Xenopus laevis. Pdgf‐b morphants showed NCC migration defects and morphological alterations of craniofacial skeletal elements and cranial nerves. Mesencephalic NCC derivatives are specifically affected in Pdgf‐b morphants. Pdgf‐b seems to be necessary for the correct gene expression of cadherin 6 and cadherin 11 during craniofacial development.