Reelin signaling directly affects radial glia morphology and biochemical maturation.
Radial glial cells are characterized, besides their astroglial properties, by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1-/- mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.
Hartfuss
Eva
E
Max-Planck-Institute of Neurobiology, Neuronal Specification, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Förster
Eckart
E
Bock
Hans H
HH
Hack
Michael A
MA
Leprince
Pierre
P
Luque
Juan M
JM
Herz
Joachim
J
Frotscher
Michael
M
Götz
Magdalena
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002454:Cell Differentiation; D048429:Cell Size; D022081:Cell Surface Extensions / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases