期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 22, 页码 5817-5826出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0853-08.2008
关键词
GPR56; bilateral frontoparietal polymicrogyria; BFPP; basement membrane; cobblestone cortex; cortical lamination
资金
- NICHD NIH HHS [P30-HD 18655, P30 HD018655] Funding Source: Medline
- NINDS NIH HHS [R01 NS035884, T32 NS007484-06, R01 NS057536, T32 NS007484, K08 NS045762, R01 NS35884, K08 NS045762-01A1, R01 NS057536-01A1] Funding Source: Medline
GPR56 is a member of the family of adhesion G-protein-coupled receptors that have a large extracellular region containing a GPS (G-protein proteolytic site) domain. Loss-of-function mutations in the GPR56 gene cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). BFPP is a radiological diagnosis and its histopathology remains unclear. This study demonstrates that loss of the mouse Gpr56 gene leads to neuronal ectopia in the cerebral cortex, a cobblestone-like cortical malformation. There are four crucial events in the development of cobblestone cortex, namely defective pial basement membrane (BM), abnormal anchorage of radial glial endfeet, mislocalized Cajal -Retzius cells, and neuronal overmigration. By detailed time course analysis, we reveal that the leading causal events are likely the breaches in the pial BM. We show further that GPR56 is present in abundance in radial glial endfeet. Furthermore, a putative ligand of GPR56 is localized in the marginal zone or overlying extracellular matrix. These observations provide compelling evidence that GPR56 functions in regulating pial BM integrity during cortical development.
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