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Published on: April 3, 2013
GPR56 functions together with α3β1 integrin in regulating cerebral cortical development
Sung-Jin Jeong1, Rong Luo, Kathleen Singer
1Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Plos One
|July 23, 2013
Summary
Loss of function mutations in G protein-coupled receptor 56 (GPR56) cause brain malformations. This study reveals GPR56 and α3β1 integrin synergistically regulate cerebral cortex development by maintaining the pial basement membrane.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- G protein-coupled receptor 56 (GPR56) mutations cause bilateral frontoparietal polymicrogyria (BFPP), a human brain malformation.
- GPR56 deletion in mice leads to breaches in the pial basement membrane and neuronal ectopias during cortical development.
- α3β1 integrin is known to be involved in the assembly and maintenance of the pial basement membrane.
Purpose of the Study:
- To investigate the potential synergistic role of GPR56 and α3β1 integrin in cerebral cortical development.
- To determine if α3β1 integrin functions with GPR56 in regulating the pial basement membrane.
Main Methods:
- Utilized Gpr56 knockout mouse models.
- Generated double knockout mice lacking both Gpr56 and α3 integrin.
- Examined cerebral cortical development and pial basement membrane integrity in these models.
Main Results:
- Loss of α3 integrin exacerbates the cortical phenotype observed in Gpr56 deletion.
- Neuronal overmigration through a breached pial basement membrane occurs earlier in double knockout mice compared to Gpr56 single knockout mice.
- Demonstrated functional synergism between GPR56 and α3β1 integrin.
Conclusions:
- GPR56 and α3β1 integrin act synergistically to regulate cerebral cortical development.
- Both proteins are crucial for the proper assembly and maintenance of the pial basement membrane.
- Disruption of this synergistic interaction leads to enhanced brain malformations.
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