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Published on: March 20, 2014
G protein-coupled receptor-dependent development of human frontal cortex
Xianhua Piao1, R Sean Hill, Adria Bodell
1Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Mutations in GPR56, a G protein-coupled receptor (GPCR), cause bilateral frontoparietal polymicrogyria (BFPP), a human brain malformation. This highlights GPCR signaling
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The mammalian cerebral cortex exhibits species-specific anatomical and functional organization.
- The molecular mechanisms underlying cortical functional subdivision remain largely unknown.
Purpose of the Study:
- To investigate the molecular basis of human brain cortical development and malformations.
- To identify genes involved in the regional development of the cerebral cortex.
Main Methods:
- Genetic analysis of patients with bilateral frontoparietal polymicrogyria (BFPP).
- Characterization of GPR56 (an orphan G protein-coupled receptor) function in cortical development.
Main Results:
- Mutations in GPR56 were identified as the cause of BFPP, a human brain cortical malformation.
- BFPP is characterized by disorganized cortical lamination, most severe in the frontal cortex.
- GPR56 encodes an orphan G protein-coupled receptor with a large extracellular domain.
Conclusions:
- GPCR signaling is essential for the regional development of the human cerebral cortex.
- GPR56 plays a critical role in establishing normal cortical structure.
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