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

Biol Open. 2022 Aug 15;11(8):bio059431. doi: 10.1242/bio.059431. Epub 2022 Aug 9.

Abstract

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 (PDGF-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 in a human neuroimaging pattern called Dandy Walker malformation. Pdgfc-Pdgfra mutant mice also display ependymal denudation in the fourth ventricle and gene expression changes in cerebellar meninges, which coincide with the first visible signs of cerebellar malformation. Here, we show that PDGF-C/PDGFRα signalling is a critical component in 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.

Keywords: Cerebellum; Dandy Walker malformation; Malformation; PDGF-C; PDGFR-alfa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / growth & development*
  • Dandy-Walker Syndrome / diagnosis
  • Dandy-Walker Syndrome / genetics
  • Humans
  • Lymphokines
  • Mice
  • Nervous System Malformations* / genetics
  • Platelet-Derived Growth Factor / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Signal Transduction*

Substances

  • Lymphokines
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor C
  • Receptor, Platelet-Derived Growth Factor alpha