Cited by 241Neurogenesis and neuroplasticity mechanismsFetal and Pediatric Neurological DisordersGenetics and Neurodevelopmental Disorders

GPR56 Regulates Pial Basement Membrane Integrity and Cortical Lamination

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Li, Shihong, Jin, Zhaohui, Koirala, Samir, Bu, Lihong, Xu, Lei, Hynes, Richard O., Walsh, Christopher A., Corfas, Gabriel +1 more·2008·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.0853-08.2008

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Authors
Li, S., Jin, Z., Koirala, S., Bu, L., Xu, L., Hynes, R. O., Walsh, C. A., Corfas, G., & Piao, X.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
  • Beth Israel Deaconess Medical Center (US)
Venue
The Journal of Neuroscience
Published
2008-05-28
Volume
28
Issue
22
Pages
5817-5826
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2065631407
Cited by
241
References
37
Citations by year
2026: 10 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 7 · 2020: 16 · 2019: 15 · 2018: 8 · 2017: 9 · 2016: 16 · 2015: 19 · 2014: 16 · 2013: 17 · 2012: 16
FWCI
5.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Charles H. Hood Foundation
  • Flight Attendant Medical Research Institute
  • National Institutes of Health
  • Genentech
  • National Institute of Neurological Disorders and Stroke (R01 NS35884, R01NS057536, K08NS045762, T32NS007484, R01NS035884)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
GPR56, adhesion G protein-coupled receptors, cortical lamination, Cajal-Retzius cells, cortical development, extracellular matrix
MeSH terms
Animals, Animals, Newborn, Bacterial Outer Membrane Proteins, Basement Membrane, Bromodeoxyuridine, Cell Movement, Cerebral Cortex, Embryo, Mammalian, Mutation, Neuroglia, Neurons, Pia Mater, Stem Cells, Tubulin, Mice, Knockout, Gene Expression Regulation, Developmental, ATP-Binding Cassette Transporters, Lamins, Receptors, G-Protein-Coupled, Mice

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