GPR56 functions together with ?3?1 integrin in regulating cerebral cortical development.

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 ?3?1 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 ?3 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 ?3?1 integrin in regulating the development of cerebral cortex.

SUBMITTER: Jeong SJ 

PROVIDER: S-EPMC3706371 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature