Reelin, Disabled 1, and beta 1 integrins are required for the formation of the radial glial scaffold in the hippocampus.
The extracellular matrix molecule Reelin is required for the correct positioning of neurons during the development of the forebrain. However, the mechanism of Reelin action on neuronal migration is poorly understood. Reelin is assumed to act on neurons directly, but it may also affect the differentiation of glial cells necessary for neuronal migration. Here we show that a regular glial scaffold fails to form in vivo in the dentate gyrus of mice deficient of Reelin or Disabled 1, a neuronal adaptor protein in the Reelin signaling pathway. A subset of these defects is observed in mice that lack beta(1)-class integrins, known to bind Reelin. Moreover, recombinant Reelin induced branching of glial processes in vitro. Our data suggest that Reelin affects glial differentiation via Disabled 1 and beta(1)-class integrin-dependent signaling pathways.
Förster
Eckart
E
Anatomisches Institut, Universität Freiburg, P.O. Box 111, D-79001 Freiburg, Germany. foerster@uni-feiburg.de
Tielsch
Albrecht
A
Saum
Barbara
B
Weiss
Karl Heinz
KH
Johanssen
Celine
C
Graus-Porta
Diana
D
Müller
Ulrich
U
Frotscher
Michael
M
D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006056:Golgi Apparatus / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D016548:Prosencephalon / Q000254:growth & development / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction
D015816:Cell Adhesion Molecules, Neuronal; D018076:DNA, Complementary; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D005904:Glial Fibrillary Acidic Protein; D019012:Integrin beta1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases