Cerebral Cortex, Vol. 13, No. 6, 634-640,
June 2003
© 2003 Oxford University Press
Reelin Controls Granule Cell Migration in the Dentate Gyrus by Acting on the Radial Glial Scaffold
Anatomisches Institut, Universität Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany
Address correspondence to Michael Frotscher, Anatomisches Institut, Albert-Ludwigs-Universität Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany. Email: michael.frotscher{at}anat.uni-freiburg.de.
Reelin, synthesized and secreted by Cajal–Retzius (CR) cells in the marginal zone of the cortex, is an extracellular matrix protein important for the development of cortical layers. In reeler mutant mice lacking Reelin, there are severe malformations of neocortical and hippocampal lamination. It has been assumed that Reelin acts as a stop signal for migrating neurons. Here we show, by using the dentate gyrus as a model in in vivo studies and in vitro assays, that Reelin exerts its effects, at least in part, by acting on the radial glial scaffold required for neuronal migration. Migration defects of dentate granule cells, reminiscent of those seen in reeler mutants, are observed in tissue from patients with temporal lobe epilepsy (TLE). The extent of granule cell dispersion in TLE was found to be inversely correlated with the number of reelin mRNA synthesizing CR cells and reelin mRNA expression as revealed in quantitative RT–PCR studies. These findings show that the Reelin signaling pathway is essential for the correct positioning of human hippocampal neurons and that a Reelin deficiency is involved in the pathological changes associated with epilepsy.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Barry, M. Piper, C. Lindwall, R. Moldrich, S. Mason, E. Little, A. Sarkar, S. Tole, R. M. Gronostajski, and L. J. Richards Specific Glial Populations Regulate Hippocampal Morphogenesis J. Neurosci., November 19, 2008; 28(47): 12328 - 12340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kerjan and J. G. Gleeson A missed exit: Reelin sets in motion Dab1 polyubiquitination to put the break on neuronal migration Genes & Dev., November 15, 2007; 21(22): 2850 - 2854. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Qiu and E. J. Weeber Reelin Signaling Facilitates Maturation of CA1 Glutamatergic Synapses J Neurophysiol, March 1, 2007; 97(3): 2312 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Favor, C. J. Gloeckner, D. Janik, M. Klempt, A. Neuhauser-Klaus, W. Pretsch, W. Schmahl, and L. Quintanilla-Fend Type IV Procollagen Missense Mutations Associated With Defects of the Eye, Vascular Stability, the Brain, Kidney Function and Embryonic or Postnatal Viability in the Mouse, Mus musculus: An Extension of the Col4a1 Allelic Series and the Identification of the First Two Col4a2 Mutant Alleles Genetics, February 1, 2007; 175(2): 725 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Haubst, E. Georges-Labouesse, A. De Arcangelis, U. Mayer, and M. Gotz Basement membrane attachment is dispensable for radial glial cell fate and for proliferation, but affects positioning of neuronal subtypes Development, August 15, 2006; 133(16): 3245 - 3254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Heinrich, N. Nitta, A. Flubacher, M. Muller, A. Fahrner, M. Kirsch, T. Freiman, F. Suzuki, A. Depaulis, M. Frotscher, et al. Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus. J. Neurosci., April 26, 2006; 26(17): 4701 - 4713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Beffert, A. Durudas, E. J. Weeber, P. C. Stolt, K. M. Giehl, J. D. Sweatt, R. E. Hammer, and J. Herz Functional Dissection of Reelin Signaling by Site-Directed Disruption of Disabled-1 Adaptor Binding to Apolipoprotein E Receptor 2: Distinct Roles in Development and Synaptic Plasticity J. Neurosci., February 15, 2006; 26(7): 2041 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thom, J. Zhou, L. Martinian, and S. Sisodiya Quantitative post-mortem study of the hippocampus in chronic epilepsy: seizures do not inevitably cause neuronal loss Brain, June 1, 2005; 128(6): 1344 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Kim, R. Koyama, R. X. Yamada, M. K. Yamada, N. Nishiyama, N. Matsuki, and Y. Ikegaya Environmental Control of the Survival and Differentiation of Dentate Granule Neurons Cereb Cortex, December 1, 2004; 14(12): 1358 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Meyer, A. C. Socorro, C. G. P. Garcia, L. M. Millan, N. Walker, and D. Caput Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning J. Neurosci., November 3, 2004; 24(44): 9878 - 9887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhao, X. Chai, E. Forster, and M. Frotscher Reelin is a positional signal for the lamination of dentate granule cells Development, October 15, 2004; 131(20): 5117 - 5125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Abraham, C. G. Perez-Garcia, and G. Meyer p73 and Reelin in Cajal-Retzius Cells of the Developing Human Hippocampal Formation Cereb Cortex, May 1, 2004; 14(5): 484 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Arnaud, B. A. Ballif, and J. A. Cooper Regulation of Protein Tyrosine Kinase Signaling by Substrate Degradation during Brain Development Mol. Cell. Biol., December 15, 2003; 23(24): 9293 - 9302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hartfuss, E. Forster, H. H. Bock, M. A. Hack, P. Leprince, J. M. Luque, J. Herz, M. Frotscher, and M. Gotz Reelin signaling directly affects radial glia morphology and biochemical maturation Development, October 1, 2003; 130(19): 4597 - 4609. [Abstract] [Full Text] [PDF]
|
|