A role for PDGF-C/PDGFRα signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex

Johanna Andrae; Leonor Gouveia; Radiosa Gallini; Liqun He; Linda Fredriksson; Ingrid Nilsson; Bengt R Johansson; Ulf Eriksson; Christer Betsholtz

doi:10.1242/bio.017368

A role for PDGF-C/PDGFRα signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex

Biol Open. 2016 Apr 15;5(4):461-74. doi: 10.1242/bio.017368.

Authors

Johanna Andrae¹, Leonor Gouveia², Radiosa Gallini³, Liqun He², Linda Fredriksson³, Ingrid Nilsson³, Bengt R Johansson⁴, Ulf Eriksson³, Christer Betsholtz²

Affiliations

¹ Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 751 85, Sweden johanna.andrae@igp.uu.se.
² Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 751 85, Sweden.
³ Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 171 77, Sweden.
⁴ The Electron Microscopy Unit, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg 405 30, Sweden.

Abstract

Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFRα. Analysis ofPdgfcnull mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFRα ligands might obscure additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants forPdgfc(-/-)andPdgfra(GFP/+) These mice display a range of severe phenotypes including spina bifida, lung emphysema, abnormal meninges and neuronal over-migration in the cerebral cortex. 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. We also present expression data onPdgfa,PdgfcandPdgfrain the cerebral cortex and microarray data on cerebral meninges.

Keywords: Basement membrane; Cerebrum; Meninges; PDGF-C; PDGFRα.