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Published on: May 8, 2020
GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration
Kathleen Singer1, Rong Luo, Sung-Jin Jeong
1Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
Insights
GPR56 protein is crucial for brain development. Its ligand, Collagen III, activates a pathway essential for preventing cortical malformations like bilateral frontoparietal polymicrogyria (BFPP).
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- GPR56 is an adhesion G protein-coupled receptor (GPCR) involved in cortical development.
- Mutations in GPR56 lead to bilateral frontoparietal polymicrogyria (BFPP), a cortical malformation.
- GPR56 has transitioned from an uncharacterized protein to a well-understood receptor.
Purpose of the Study:
- To elucidate the specific role of GPR56 in the developing brain.
- To understand the signaling pathway activated by GPR56.
- To investigate the critical function of GPR56 in preplate neurons.
Main Methods:
- The study focuses on the interaction between GPR56 and its ligand, Collagen III.
- It examines the GPR56 signaling pathway involving RhoA activation via Gα(12/13) coupling.
- Expression patterns of GPR56 in preplate neurons were analyzed in relation to malformation gradients.
Main Results:
- Collagen III is identified as the ligand for GPR56 in the developing brain.
- GPR56 activation by Collagen III triggers the RhoA/Gα(12/13) signaling pathway.
- GPR56 expression in preplate neurons correlates with the anterior-to-posterior gradient of BFPP observed in humans and mice.
Conclusions:
- GPR56 signaling is critical for proper cortical development and patterning.
- The GPR56 pathway in preplate neurons is essential for preventing neuronal migration defects.
- Further research into GPR56 in preplate neurons will illuminate mechanisms of cortical patterning.
Abstract:
GPR56, a member of the adhesion G protein-coupled receptor (GPCR) family, is integral to the development of the cortex, as mutations in GPR56 cause bilateral frontoparietal polymicrogyria (BFPP). BFPP is a cobblestone-like cortical malformation, characterized by overmigrating neurons and the formation of neuronal ectopias on the surface of the brain. Since its original cloning a decade ago, GPR56 has emerged from an orphaned and uncharacterized protein to an increasingly well-understood receptor, both in terms of its signaling and function. Collagen III is the ligand of GPR56 in the developing brain. Upon binding to collagen III, GPR56 activates RhoA via coupling to Gα(12/13). This pathway appears to be particularly critical in the preplate neurons, which are the earliest born neurons in the cortex, as the expression pattern of GPR56 in these neurons mimics the anterior to posterior gradient of malformation associated with loss of GPR56 in both humans and mice. Further characterizing the role of GPR56 in the preplate will shed light on the mechanism of cortical development and patterning.
