GPR56 functions together with α3β1 integrin in regulating cerebral cortical development

PLoS One. 2013 Jul 9;8(7):e68781. doi: 10.1371/journal.pone.0068781. Print 2013.

Abstract

Loss of function mutations in GPR56, which encodes a G protein-coupled receptor, cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Studies from BFPP postmortem brain tissue and Gpr56 knockout mice have previously showed that GPR56 deletion leads to breaches in the pial basement membrane (BM) and neuronal ectopias during cerebral cortical development. Since α3β1 integrin also plays a role in pial BM assembly and maintenance, we evaluated whether it functions together with GPR56 in regulating the same developmental process. We reveal that loss of α3 integrin enhances the cortical phenotype associated with Gpr56 deletion, and that neuronal overmigration through a breached pial BM occurs earlier in double knockout than in Gpr56 single knockout mice. These observations provide compelling evidence of the synergism of GPR56 and α3β1 integrin in regulating the development of cerebral cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Cell Movement / genetics
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Collagen Type III / metabolism
  • Gene Deletion
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / metabolism
  • Phenotype
  • Protein Binding
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Collagen Type III
  • GPR56 protein, mouse
  • Integrin alpha3beta1
  • Receptors, G-Protein-Coupled