G protein-coupled receptor-dependent development of human frontal cortex.
The mammalian cerebral cortex is characterized by complex patterns of anatomical and functional areas that differ markedly between species, but the molecular basis for this functional subdivision is largely unknown. Here, we show that mutations in GPR56, which encodes an orphan G protein-coupled receptor (GPCR) with a large extracellular domain, cause a human brain cortical malformation called bilateral frontoparietal polymicrogyria (BFPP). BFPP is characterized by disorganized cortical lamination that is most severe in frontal cortex. Our data suggest that GPCR signaling plays an essential role in regional development of human cerebral cortex.
Piao
Xianhua
X
Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Hill
R Sean
RS
Bodell
Adria
A
Chang
Bernard S
BS
Basel-Vanagaite
Lina
L
Straussberg
Rachel
R
Dobyns
William B
WB
Qasrawi
Bassam
B
Winter
Robin M
RM
Innes
A Micheil
AM
Voit
Thomas
T
Ross
M Elizabeth
ME
Michaud
Jacques L
JL
Déscarie
Jean-Claude
JC
Barkovich
A James
AJ
Walsh
Christopher A
CA
D019943:Amino Acid Substitution; D000818:Animals; D016375:Antisense Elements (Genetics); D005075:Biological Evolution; D019521:Body Patterning; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D005260:Female; D016368:Frameshift Mutation; D005625:Frontal Lobe / Q000002:abnormalities* / Q000196:embryology; D023061:Gene Order; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D009474:Neurons / Q000502:physiology; D010296:Parietal Lobe / Q000002:abnormalities / Q000196:embryology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology
C118925:ADGRG1 protein, human; D016375:Antisense Elements (Genetics); D008024:Ligands; D043562:Receptors, G-Protein-Coupled