Dandy Walker-like malformations in mutant mice demonstrate a role for PDGF-C/PDGFRα signalling in cerebellar development

Formation of the mouse cerebellum is initiated in the embryo and continues for a few weeks after birth. Double mutant mice lacking platelet-derived growth factor-C and that are heterozygous for platelet-derived growth factor receptor alpha (Pdgfc-/-; PdgfraGFP/+) develop cerebellar hypoplasia and malformation with loss of cerebellar lobes in the posterior vermis. This phenotype is similar to those observed in Foxc1 mutant mice and the human syndrome Dandy Walker malformation. Pdgfc-Pdgfra mutant mice also display ependymal denudation in the 4th ventricle and gene expression changes in cerebellar meninges, which coincide with the first visible signs of cerebellar malformation. Our observations suggest that PDGF-C/PDGFR signalling is a critical component of the network of molecular and cellular interactions that take place between the developing meninges and neural tissues, and which are required to build a fully functioning cerebellum. Summary statementMice lacking PDGF-C develop cerebellar hypoplasia and malformation. In addition, the ventricular zone close to the rhombic lip suffer from ependymal denudation.