Abstract
Mutations in the Platelet-derived growth factor alpha-receptor (pdgfalpha) gene lead to neural crest-associated defects and suggest that associations between PDGFRalpha and its ligand, Platelet-derived growth factor A-chain (PDGFA) are required for neural crest cell development. However, the lethality of this mutation and its accompanying somite and neural tube defects has hindered attempts to define the function of these proteins. To test whether PDGFA influences neural crest cell migration, survival or proliferation, mice were genetically engineered to ectopically express PDGFA. The introduced mutation was partially lethal, however, embryos did not have somite or neural tube defects. Mutant mice appeared grossly normal, but suffered a late-onset deterioration of sympathetic ganglia with perineurial cell invasion, reminiscent of intraneural perineuriomas and neuritic dystrophies. Therefore, PDGFA may promote movement or proliferation of perineurial cells. During embryonic development, ectopic expression of PDGFA altered the temporal and spatial distribution of neural crest cells within the branchial arches and circumpharyngeal regions, but not their survival, proliferation, motility, or differentiation between E9.5--11.5. Patterning of neural sub-populations of neural crest was unaltered. Thus, PDGFA influences the development of non-neuronal neural crest cells directly, and argues that one activity of PDGFA in vivo is to provide spatial cues to migrating neural crest cells during embryogenesis.