Cerebellar gene expression changes in Pdgfc and Pdgfra mutant

Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFR-alpha. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFR-alpha ligands might hide additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc -/- and Pdgfra GFP/+. These mice display a range of severe phenotypes including cerebellar malformation, neuronal over-migration in the cerebral cortex, spina bifida and lung emphysema. We focused our analysis on the central nervous system (CNS), where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane. Cerebellum from E13.5 and E14.5 embryos were freely dissected. Tissues were stored in RNA later® (Ambion), RNA was isolated using RNeasy micro kit (Qiagen) and quality checked in a 2100 BioAnalyzer (Agilent Technologies, Santa Clara, CA, USA). Transcription profiling was performed with Gene Chip Mouse Gene 1.0 ST array. We compared mice with a cerebellar phenotype (Pdgfc-/-; Pdgfra GFP/+) with a control group consisting of all littermates (Pdgfc+/+, Pdgfc+/-, Pdgfc-/-, Pdgfc+/+; Pdgfra GFP/+ and Pdgfc+/-; Pdgfra GFP/+). One litter from E13.5 (3 mutants and 5 controls) and one litter from E14.5 (2 mutants and 7 controls) were used.