Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex.
Mice that lack all beta1-class integrins in neurons and glia die prematurely after birth with severe brain malformations. Cortical hemispheres and cerebellar folia fuse, and cortical laminae are perturbed. These defects result from disorganization of the cortical marginal zone, where beta1-class integrins regulate glial endfeet anchorage, meningeal basement membrane remodeling, and formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins are not essential for neuron-glia interactions and neuronal migration during corticogenesis. The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.
Graus-Porta
D
D
Friedrich Miescher Institute, Maulbeerstr 66, 4058, Basel, Switzerland.
Blaess
S
S
Senften
M
M
Littlewood-Evans
A
A
Damsky
C
C
Huang
Z
Z
Orban
P
P
Klein
R
R
Schittny
J C
JC
Müller
U
U
D000818:Animals; D001921:Brain / Q000002:abnormalities*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000235:genetics
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000091042:Reelin Protein; D001616:beta-Galactosidase; D012697:Serine Endopeptidases