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FAK Deficiency in Cells Contributing to the Basal Lamina Results in Cortical Abnormalities Resembling Congenital Muscular Dystrophies

FAK Deficiency in Cells Contributing to the Basal Lamina Results in Cortical Abnormalities Resembling Congenital Muscular Dystrophies
Targeted deletion of focal adhesion kinase (fak) in the developing dorsal forebrain resulted in local disruptions of the cortical basement membrane located between the neuroepithelium and pia-meninges. At disruption sites, clusters of neurons invaded the marginal zone. Retraction of radial glial endfeet, midline fusion of brain hemispheres, and gliosis also occurred, similar to type II cobblestone lissencephaly as seen in congenital muscular dystrophy. Interestingly, targeted deletion of fak in neurons alone did not result in cortical ectopias, indicating that fak deletion from glia is required for neuronal mislocalization. Unexpectedly, fak deletion specifically from meningeal fibroblasts elicited similar cortical ectopias in vivo and altered laminin organization in vitro. These observations provide compelling evidence that FAK plays a key signaling role in cortical basement membrane assembly and/or remodeling. In addition, FAK is required within neurons during development because neuron-specific fak deletion alters dendritic morphology in the absence of lamination defects.
- Max Planck Society Germany
- University of California System United States
- University of California, San Francisco United States
- University of Colorado System United States
- University of Colorado Boulder United States
Cerebral Cortex, Calbindins, Extracellular Matrix Proteins, Neuroscience(all), Cell Adhesion Molecules, Neuronal, Blotting, Western, Fibroblasts, Embryo, Mammalian, Basement Membrane, DNA-Binding Proteins, Cytoskeletal Proteins, Disease Models, Animal, Bacterial Proteins, Astrocytes, Calbindin 2, Focal Adhesion Kinase 1, Animals, Dura Mater, Carrier Proteins, Dystroglycans, Cells, Cultured
Cerebral Cortex, Calbindins, Extracellular Matrix Proteins, Neuroscience(all), Cell Adhesion Molecules, Neuronal, Blotting, Western, Fibroblasts, Embryo, Mammalian, Basement Membrane, DNA-Binding Proteins, Cytoskeletal Proteins, Disease Models, Animal, Bacterial Proteins, Astrocytes, Calbindin 2, Focal Adhesion Kinase 1, Animals, Dura Mater, Carrier Proteins, Dystroglycans, Cells, Cultured
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