The extracellular protein Reelin was initially identified as an essential factor in the control of neuronal migration and layer formation in the developing mammalian brain. In the years following its discovery, however, it became clear that Reelin is a multifunctional protein that controls not only the positioning of neurons in the developing brain, but also their growth, maturation, and synaptic activity in the adult brain. In this review, we will highlight the major discoveries of the biological activities of Reelin and the underlying molecular mechanisms that affect the development and function of the mammalian brain, from embryonic ages to adulthood. 1. The reeler Mouse and Reelin Gene Discovery Reelin was identified in 1995 as the gene disrupted in two mouse strains carrying the autosomal recessive mutation reeler, a transgenic and a spontaneous strain that originated in Edinburgh [1]. While a newly generated transgenic strain was instrumental in the cloning of the gene, the classic, spontaneous Edinburgh reeler mutant strain had been well known for decades to developmental neurobiologists for the distinct neurological phenotype observed in homozygous mice, which includes tremors, ataxia, cerebellar hypoplasia, and widespread disruption of cellular layers throughout the brain [2–10]. Upon cloning and mapping of the gene, it turned out that a large deletion in the Reelin gene had occurred in the Edinburgh strain, resulting in the complete loss of transcript expression [1]. Around the same time, a portion of the Reelin coding sequence was also identified in another spontaneous reeler strain that originated in Orleans [11]. In this strain, however, a truncated transcript predicted to encode a C terminal deletion mutant protein was stably expressed. To date, several additional reeler mouse mutant strains carrying mutations in the Reelin gene have been identified, all resulting in the loss of transcript expression. Like the original Edinburgh mutation (now called B6C3Fe ala-Relnrl/J), these strains exhibit essentially the same reeler phenotype and are made commercially available from The Jackson Laboratory. As Reelin gene orthologs were identified in other vertebrate species, other reeler-like mutations were quickly characterized. In the rat, for example, two mutant strains, the Shaking Rat Kawasaki and the Komed Zucker Creeping rat, that exhibited a reeler-like phenotype were reported to carry Reelin gene mutation [12, 13]. The human REELIN gene was also quickly cloned [14], and human subjects carrying REELIN mutations in homozygousity were identified
References
[1]
G. D'Arcangelo, G. G. Miao, S.-C. Chen, H. D. Soares, J. I. Morgan, and T. Curran, “A protein related to extracellular matrix proteins deleted in the mouse mutant reeler,” Nature, vol. 374, no. 6524, pp. 719–723, 1995.
[2]
J. B. Angevine Jr. and R. L. Sidman, “Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse,” Nature, vol. 192, no. 4804, pp. 766–768, 1961.
[3]
V. S. Caviness Jr. and P. Rakic, “Mechanisms of cortical development: a view from mutations in mice,” Annual Review of Neuroscience, vol. 1, pp. 297–326, 1978.
[4]
D. S. Falconer, “Two new mutants, “trembler” and “reeler”, with neurological actions in the house mouse (Mus musculus L.),” Journal of Genetics, vol. 50, no. 2, pp. 192–205, 1951.
[5]
A. M. Goffinet, “Events governing organization of postmigratory neurons: studies on brain development in normal and reeler mice,” Brain Research, vol. 319, no. 3, pp. 261–296, 1984.
[6]
C. Lambert de Rouvroit and A. M. Goffinet, “The reeler mouse as a model of brain development,” Advances in Anatomy, Embryology, and Cell Biology, vol. 150, pp. 1–106, 1998.
[7]
J. Mariani, F. Crepel, K. Mikoshiba, J. P. Changeux, and C. Sotelo, “Anatomical, physiological and biochemical studies of the cerebellum from Reeler mutant mouse,” Philosophical Transactions of the Royal Society of London. Series B, vol. 281, no. 978, pp. 1–28, 1977.
[8]
K. Mikoshiba, S. Kohsaka, and K. Takamatsu, “Morphological and biochemical studies on the cerebral cortex from reeler mutant mice: development of cortical layers and metabolic mapping by the deoxyglucose method,” Journal of Neurochemistry, vol. 34, no. 4, pp. 835–844, 1980.
[9]
M. C. Pinto Lord, P. Evrard, and V. S. Caviness Jr., “Obstructed neuronal migration along radial glial fibers in the neocortex of the Reeler mouse: a Golgi-EM analysis,” Developmental Brain Research, vol. 4, no. 4, pp. 379–393, 1982.
[10]
P. Rakic and V. S. Caviness Jr., “Cortical development: view from neurological mutants two decades later,” Neuron, vol. 14, no. 6, pp. 1101–1104, 1995.
[11]
S. Hirotsune, T. Takahara, N. Sasaki et al., “The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons,” Nature Genetics, vol. 10, no. 1, pp. 77–83, 1995.
[12]
S. Kikkawa, T. Yamamoto, K. Misaki et al., “Missplicing resulting from a short deletion in the reelin gene causes reeler-like neuronal disorders in the mutant shaking rat Kawasaki,” Journal of Comparative Neurology, vol. 463, no. 3, pp. 303–315, 2003.
[13]
N. Yokoi, M. Namae, H.-Y. Wang et al., “Rat neurological disease creeping is caused by a mutation in the reelin gene,” Molecular Brain Research, vol. 112, no. 1-2, pp. 1–7, 2003.
[14]
U. DeSilva, G. D'Arcangelo, V. V. Braden et al., “The human reelin gene: isolation, sequencing, and mapping on chromosome 7,” Genome Research, vol. 7, no. 2, pp. 157–164, 1997.
[15]
S. E. Hong, Y. Y. Shugart, D. T. Huang et al., “Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations,” Nature Genetics, vol. 26, no. 1, pp. 93–96, 2000.
[16]
P. E. Phelps, R. Rich, S. Dupuy-Davies, Y. Ríos, and T. Wong, “Evidence for a cell-specific action of Reelin in the spinal cord,” Developmental Biology, vol. 244, no. 1, pp. 180–198, 2002.
[17]
M. D. Kubasak, R. Brooks, S. Chen, S. A. Villeda, and P. E. Phelps, “Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord,” Journal of Comparative Neurology, vol. 468, no. 2, pp. 165–178, 2004.
[18]
J. W. Yip, Y. P. L. Yip, K. Nakajima, and C. Capriotti, “Reelin controls position of autonomic neurons in the spinal cord,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 15, pp. 8612–8616, 2000.
[19]
D. S. Rice, S. Nusinowitz, A. M. Azimi, A. Martínez, E. Soriano, and T. Curran, “The Reelin pathway modulates the structure and fof retinal synaptic circuitry,” Neuron, vol. 31, no. 6, pp. 929–941, 2001.
[20]
J. A. Del Río, B. Heimrich, V. Borrell et al., “A role for Cajal-retzius cells and reelin in the development of hippocampal connections,” Nature, vol. 385, no. 6611, pp. 70–74, 1997.
[21]
T. Deller, A. Drakew, B. Heimrich, E. F？rster, A. Tielsch, and M. Frotscher, “The hippocampus of the reeler mutant mouse: fiber segregation in area CA1 depends on the position of the postsynaptic target cells,” Experimental Neurology, vol. 156, no. 2, pp. 254–267, 1999.
[22]
I. Royaux, C. L. De Rouvroit, G. D'Arcangelo, D. Demirov, and A. M. Goffinet, “Genomic organization of the mouse reelin gene,” Genomics, vol. 46, no. 2, pp. 240–250, 1997.
[23]
Y. Chen, R. P. Sharma, R. H. Costa, E. Costa, and D. R. Grayson, “On the epigenetic regulation of the human reelin promoter,” Nucleic Acids Research, vol. 30, no. 13, pp. 2930–2939, 2002.
[24]
C. P. Mitchell, Y. Chen, M. Kundakovic, E. Costa, and D. R. Grayson, “Histone deacetylase inhibitors decrease reelin promoter methylation in vitro,” Journal of Neurochemistry, vol. 93, no. 2, pp. 483–492, 2005.
[25]
F. Impagnatiello, A. R. Guidotti, C. Pesold et al., “A decrease of reelin expression as a putative vulnerability factor in schizophrenia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 26, pp. 15718–15723, 1998.
[26]
A. Guidotti, J. Auta, J. M. Davis et al., “Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study,” Archives of General Psychiatry, vol. 57, no. 11, pp. 1061–1069, 2000.
[27]
S. H. Fatemi, “The role of Reelin in pathology of autism,” Molecular Psychiatry, vol. 7, no. 9, pp. 919–920, 2002.
[28]
T. D. Folsom and S. H. Fatemi, “The involvement of Reelin in neurodevelopmental disorders,” Neuropharmacology, vol. 68, pp. 122–135, 2012.
[29]
D. R. Grayson, Y. Chen, E. Costa et al., “The human reelin gene: transcription factors (+), repressors (？) and the methylation switch (+/？) in schizophrenia,” Pharmacology and Therapeutics, vol. 111, no. 1, pp. 272–286, 2006.
[30]
A. Guidotti, J. Auta, J. M. Davis et al., “GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon,” Psychopharmacology, vol. 180, no. 2, pp. 191–205, 2005.
[31]
G. D'Arcangelo, K. Nakajima, T. Miyata, M. Ogawa, K. Mikoshiba, and T. Curran, “Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody,” Journal of Neuroscience, vol. 17, no. 1, pp. 23–31, 1997.
[32]
M. Ogawa, T. Miyata, K. Nakajima et al., “The realer gene-associated antigen on cajal-retzius neurons is a crucial molecule for laminar organization of cortical neurons,” Neuron, vol. 14, no. 5, pp. 899–912, 1995.
[33]
G. D'Arcangelo, R. Homayouni, L. Keshvara, D. S. Rice, M. Sheldon, and T. Curran, “Reelin is a ligand for lipoprotein receptors,” Neuron, vol. 24, no. 2, pp. 471–479, 1999.
[34]
T. Miyata, K. Nakajima, K. Mikoshiba, and M. Ogawa, “Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody,” Journal of Neuroscience, vol. 17, no. 10, pp. 3599–3609, 1997.
[35]
M. Sinagra, D. Verrier, D. Frankova et al., “Reelin, very-low-density lipoprotein receptor, and apolipoprotein E receptor 2 control somatic NMDA receptor composition during hippocampal maturation in vitro,” Journal of Neuroscience, vol. 25, no. 26, pp. 6127–6136, 2005.
[36]
K.-I. Kubo, K. Mikoshiba, and K. Nakajima, “Secreted Reelin molecules form homodimers,” Neuroscience Research, vol. 43, no. 4, pp. 381–388, 2002.
[37]
N. Yasui, T. Nogi, T. Kitao, Y. Nakano, M. Hattori, and J. Takagi, “Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 24, pp. 9988–9993, 2007.
[38]
Y. Nakano, T. Kohno, T. Hibi et al., “The extremely conserved C-terminal region of Reelin is not necessary for secretion but is required for efficient activation of downstream signaling,” Journal of Biological Chemistry, vol. 282, no. 28, pp. 20544–20552, 2007.
[39]
V. de Bergeyck, B. Naerhuyzen, A. M. Goffinet, and C. Lambert de Rouvroit, “A panel of monoclonal antibodies against reelin, the extracellular matrix protein defective in reeler mutant mice,” Journal of Neuroscience Methods, vol. 82, no. 1, pp. 17–24, 1998.
[40]
Y. Jossin, N. Ignatova, T. Hiesberger, J. Herz, C. Lambert De Rouvroit, and A. M. Goffinet, “The central fragment of Reelin, generated by proteolytic processing in vivo, is critical to its function during cortical plate development,” Journal of Neuroscience, vol. 24, no. 2, pp. 514–521, 2004.
[41]
Y. Jossin, L. Gui, and A. M. Goffinet, “Processing of Reelin by embryonic neurons is important for function in tissue but not in dissociated cultured neurons,” Journal of Neuroscience, vol. 27, no. 16, pp. 4243–4252, 2007.
[42]
N. Utsunomiya-Tate, K.-I. Kubo, S.-I. Tate et al., “Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9729–9734, 2000.
[43]
Y. Ikeda and T. Terashima, “Expression of reelin, the gene responsible for the Reeler mutation, in embryonic development and adulthood in the mouse,” Developmental Dynamics, vol. 210, pp. 157–172, 1997.
[44]
S. N. Schiffmann, “Reelin mRNA expression during mouse brain development,” European Journal of Neuroscience, vol. 9, no. 5, pp. 1055–1071, 1997.
[45]
S. Alcántara, M. Ruiz, G. D'Arcangelo et al., “Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse,” Journal of Neuroscience, vol. 18, no. 19, pp. 7779–7799, 1998.
[46]
T. Miyata, K. Nakajima, J. Aruga et al., “Distribution of the reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogenic antibody CR-50 on normal and reeler mice,” Journal of Comparative Neurology, vol. 372, pp. 215–228, 1996.
[47]
A. Drakew, M. Frotscher, T. Deller, M. Ogawa, and B. Heimrich, “Developmental distribution of a reeler gene-related antigen in the rat hippocampal formation visualized by CR-50 immunocytochemistry,” Neuroscience, vol. 82, no. 4, pp. 1079–1086, 1997.
[48]
G. Meyer, J. M. Soria, J. R. Martinez-Galan, B. Martin-Clemente, and A. Fairen, “Different origins and developmental histories of transient neurons in the marginal zone of the fetal and neonatal rat cortex,” Journal of Comparative Neurology, vol. 397, pp. 493–518, 1998.
[49]
G. Meyer and A. M. Goffinet, “Prenatal development of Reelin-immunoreactive neurons in the human neocortex,” Journal of Comparative Neurology, vol. 397, pp. 29–40, 1998.
[50]
E. F？rster, S. Zhao, and M. Frotscher, “Laminating the hippocampus,” Nature Reviews Neuroscience, vol. 7, no. 4, pp. 259–267, 2006.
[51]
V. Duveau, A. Madhusudan, M. Caleo, I. Knuesel, and J.-M. Fritschy, “Impaired reelin processing and secretion by Cajal-Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy,” Hippocampus, vol. 21, no. 9, pp. 935–944, 2011.
[52]
C. A. Haas, O. Dudeck, M. Kirsch et al., “Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy,” Journal of Neuroscience, vol. 22, no. 14, pp. 5797–5802, 2002.
[53]
C. Heinrich, N. Nitta, A. Flubacher et al., “Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus,” Journal of Neuroscience, vol. 26, no. 17, pp. 4701–4713, 2006.
[54]
A. M. Goffinet, “The embryonic development of the cerebellum in normal and reeler mutant mice,” Anatomy and Embryology, vol. 168, no. 1, pp. 73–86, 1983.
[55]
Y. Inoue, N. Maeda, T. Kokubun et al., “Architecture of Purkinje cells of the reeler mutant mouse observed by immunohistochemistry for the inositol 1,4,5-trisphoshate receptor protein P400,” Neuroscience Research, vol. 8, no. 3, pp. 189–201, 1990.
[56]
K. Mikoshiba, K. Nagaike, and S. Kohsaka, “Developmental studies on the cerebellum from reeler mutant mouse in vivo and in vitro,” Developmental Biology, vol. 79, no. 1, pp. 64–80, 1980.
[57]
M. Frotscher, “Dual role of Cajal-Retzius cells and reelin in cortisal development,” Cell and Tissue Research, vol. 290, no. 2, pp. 315–322, 1997.
[58]
V. Borrell, J. A. Del Río, S. Alcántara et al., “Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections,” Journal of Neuroscience, vol. 19, no. 4, pp. 1345–1358, 1999.
[59]
M. C. Pinto Lord and V. S. Caviness Jr., “Determinants of cell shape and orientation: a comparative Golgi analysis of cell-axon interrelationships in the developing neocortex of normal and reeler mice,” Journal of Comparative Neurology, vol. 187, no. 1, pp. 49–70, 1979.
[60]
B. B. Stanfield and W. M. Cowan, “The development of the hippocampus and dentate gyrus in normal and reeler mice,” Journal of Comparative Neurology, vol. 185, no. 3, pp. 423–459, 1979.
[61]
B. B. Stanfield and W. M. Cowan, “The morphology of the hippocampus and dentate gyrus in normal and reeler mice,” Journal of Comparative Neurology, vol. 185, no. 3, pp. 393–422, 1979.
[62]
S. Niu, A. Renfro, C. C. Quattrocchi, M. Sheldon, and G. D'Arcangelo, “Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway,” Neuron, vol. 41, no. 1, pp. 71–84, 2004.
[63]
A. J. Nichols and E. C. Olson, “Reelin promotes neuronal orientation and dendritogenesis during preplate splitting,” Cerebral Cortex, vol. 20, no. 9, pp. 2213–2223, 2010.
[64]
E. C. Olson, S. Kim, and C. A. Walsh, “Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression,” Journal of Neuroscience, vol. 26, no. 6, pp. 1767–1775, 2006.
[65]
Y. Jossin and A. M. Goffinet, “Reelin signals through phosphatidylinositol 3-kinase and Akt to control cortical development and through mTor to regulate dendritic growth,” Molecular and Cellular Biology, vol. 27, no. 20, pp. 7113–7124, 2007.
[66]
T. Matsuki, R. T. Matthews, J. A. Cooper et al., “Reelin and Stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment,” Cell, vol. 143, no. 5, pp. 826–836, 2010.
[67]
S. A. MacLaurin, T. Krucker, and K. N. Fish, “Hippocampal dendritic arbor growth in vitro: regulation by Reelin-disabled-1 signaling,” Brain Research, vol. 1172, no. 1, pp. 1–9, 2007.
[68]
C. Pesold, F. Impagnatiello, M. G. Pisu et al., “Reelin is preferentially expressed in neurons synthesizing γ-aminobutyric acid in cortex and hippocampus of adult rats,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 6, pp. 3221–3226, 1998.
[69]
O. Yabut, A. Renfro, S. Niu, J. W. Swann, O. Marín, and G. D'Arcangelo, “Abnormal laminar position and dendrite development of interneurons in the reeler forebrain,” Brain Research, vol. 1140, no. 1, pp. 75–83, 2007.
[70]
S. Niu, O. Yabut, and G. D'Arcangelo, “The reelin signaling pathway promotes dendritic spine development in hippocampal neurons,” Journal of Neuroscience, vol. 28, no. 41, pp. 10339–10348, 2008.
[71]
A. Ventruti, T. M. Kazdoba, S. Niu, and G. D'Arcangelo, “Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain,” Neuroscience, vol. 189, pp. 32–42, 2011.
[72]
V. S. Caviness Jr. and R. L. Sidman, “Time of origin or corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: an autoradiographic analysis,” Journal of Comparative Neurology, vol. 148, no. 2, pp. 141–151, 1973.
[73]
V. S. Caviness Jr., “Time of neuron origin in the hippocampus and dentate gyrus of normal and reeler mutant mice: an autoradiographic analysis,” Journal of Comparative Neurology, vol. 151, no. 2, pp. 113–120, 1973.
[74]
A. M. Goffinet, “An early developmental defect in the cerebral cortex of the reeler mouse. A morphological study leading to a hypothesis concerning the action of the mutant gene,” Anatomy and Embryology, vol. 157, no. 2, pp. 205–216, 1979.
[75]
L. Pujadas, A. Gruart, C. Bosch et al., “Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long-term potentiation,” Journal of Neuroscience, vol. 30, no. 13, pp. 4636–4649, 2010.
[76]
T. Terashima, K. Inoue, and Y. Inoue, “Observations on the cerebellum of normal-reeler mutant mouse chimera,” Journal of Comparative Neurology, vol. 252, no. 2, pp. 264–278, 1986.
[77]
K. H. Weiss, C. Johanssen, A. Tielsch et al., “Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice,” Journal of Comparative Neurology, vol. 460, no. 1, pp. 56–65, 2003.
[78]
K. E. Hunter-Schaedle, “Radial glial cell development and transformation are disturbed in reeler forebrain,” Journal of Neurobiology, vol. 33, pp. 459–472, 1997.
[79]
P. Malatesta, E. Hartfuss, and M. G？tz, “Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neural lineage,” Development, vol. 127, no. 24, pp. 5253–5263, 2000.
[80]
S. C. Noctor, A. C. Flint, T. A. Weissman, R. S. Dammerman, and A. R. Kriegstein, “Neurons derived from radial glial cells establish radial units in neocortex,” Nature, vol. 409, no. 6821, pp. 714–720, 2001.
[81]
B. Nadarajah, J. E. Brunstrom, J. Grutzendler, R. O. L. Wong, and A. L. Pearlman, “Two modes of radial migration in early development of the cerebral cortex,” Nature Neuroscience, vol. 4, no. 2, pp. 143–150, 2001.
[82]
H. Tabata and K. Nakajima, “Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex,” Journal of Neuroscience, vol. 23, no. 31, pp. 9996–10001, 2003.
[83]
I. Hack, M. Bancila, K. Loulier, P. Carroll, and H. Cremer, “Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis,” Nature Neuroscience, vol. 5, no. 10, pp. 939–945, 2002.
[84]
B. W. Howell, F. B. Gertler, and J. A. Cooper, “Mouse disabled (mDab1): a Src binding protein implicated in neuronal development,” The MBO Journal, vol. 16, no. 1, pp. 121–132, 1997.
[85]
R. Homayouni, D. S. Rice, M. Sheldon, and T. Curran, “Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1,” Journal of Neuroscience, vol. 19, no. 17, pp. 7507–7515, 1999.
[86]
B. W. Howell, L. M. Lanier, R. Frank, F. B. Gertler, and J. A. Cooper, “The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids,” Molecular and Cellular Biology, vol. 19, no. 7, pp. 5179–5188, 1999.
[87]
P. C. Stolt, H. Jeon, H. K. Song, J. Herz, M. J. Eck, and S. C. Blacklow, “Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes,” Structure, vol. 11, no. 5, pp. 569–579, 2003.
[88]
D. Goldowitz, R. C. Gushing, E. Laywell et al., “Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin,” Journal of Neuroscience, vol. 17, no. 22, pp. 8767–8777, 1997.
[89]
M. Sheldon, D. S. Rice, G. D'Arcangelo et al., “Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice,” Nature, vol. 389, no. 6652, pp. 730–733, 1997.
[90]
M. L. Ware, J. W. Fox, J. L. González et al., “Aberrant splicing of a mouse disabled homolog, mdab1, in the scrambler mouse,” Neuron, vol. 19, no. 2, pp. 239–249, 1997.
[91]
H. Yoneshima, E. Nagata, M. Matsumoto et al., “A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin,” Neuroscience Research, vol. 29, no. 3, pp. 217–223, 1997.
[92]
B. W. Howell, R. Hawkes, P. Soriano, and J. A. Cooper, “Neuronal position in the developing brain is regulated by mouse disabled-1,” Nature, vol. 389, no. 6652, pp. 733–737, 1997.
[93]
B. A. Ballif, L. Arnaud, W. T. Arthur, D. Guris, A. Imamoto, and J. A. Cooper, “Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons,” Current Biology, vol. 14, no. 7, pp. 606–610, 2004.
[94]
B. W. Howell, T. M. Herrick, and J. A. Cooper, “Reelin-induced tyrosine phosphorylation of disabled 1 during neuronal positioning,” Genes and Development, vol. 13, no. 12, pp. 643–648, 1999.
[95]
L. Keshvara, D. Benhayon, S. Magdaleno, and T. Curran, “Identification of Reelin-induced sites of tyrosyl phosphorylation on disabled 1,” Journal of Biological Chemistry, vol. 276, no. 19, pp. 16008–16014, 2001.
[96]
L. Arnaud, B. A. Ballif, E. F？rster, and J. A. Cooper, “Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development,” Current Biology, vol. 13, no. 1, pp. 9–17, 2003.
[97]
H. H. Bock and J. Herz, “Reelin activates Src family tyrosine kinases in neurons,” Current Biology, vol. 13, no. 1, pp. 18–26, 2003.
[98]
B. W. Howell, T. M. Herrick, J. D. Hildebrand, Y. Zhang, and J. A. Cooper, “Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development,” Current Biology, vol. 10, no. 15, pp. 877–885, 2000.
[99]
L. Arnaud, B. A. Ballif, and J. A. Cooper, “Regulation of protein tyrosine kinase signaling by substrate degradation during brain development,” Molecular and Cellular Biology, vol. 23, no. 24, pp. 9293–9302, 2003.
[100]
S. Suetsugu, T. Tezuka, T. Morimura et al., “Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1,” Biochemical Journal, vol. 384, no. 1, pp. 1–8, 2004.
[101]
G. Kuo, L. Arnaud, P. Kronstad-O'Brien, and J. A. Cooper, “Absence of Fyn and Src causes a Reeler-like phenotype,” Journal of Neuroscience, vol. 25, no. 37, pp. 8578–8586, 2005.
[102]
M. Trommsdorff, M. Gotthardt, T. Hiesberger et al., “Reeler/disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2,” Cell, vol. 97, no. 6, pp. 689–701, 1999.
[103]
G. D'Arcangelo, “Reelin mouse mutants as models of cortical development disorders,” Epilepsy and Behavior, vol. 8, no. 1, pp. 81–90, 2006.
[104]
L. Feng and J. A. Cooper, “Dual functions of Dab1 during brain development,” Molecular and Cellular Biology, vol. 29, no. 2, pp. 324–332, 2009.
[105]
G. Kerjan and J. G. Gleeson, “A missed exit: Reelin sets in motion Dab1 polyubiquitination to put the break on neuronal migration,” Genes and Development, vol. 21, no. 22, pp. 2850–2854, 2007.
[106]
S. Zhao and M. Frotscher, “Go or stop? Divergent roles of reelin in radial neuronal migration,” Neuroscientist, vol. 16, no. 4, pp. 421–434, 2010.
[107]
D. S. Rice, M. Sheldon, G. D'Arcangelo, K. Nakajima, D. Goldowitz, and T. Curran, “Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain,” Development, vol. 125, no. 18, pp. 3719–3729, 1998.
[108]
G. Meyer, C. L. De Rouvroit, A. M. Goffinet, and P. Wahle, “Disabled-1 mRNA and protein expression in developing human cortex,” European Journal of Neuroscience, vol. 17, no. 3, pp. 517–525, 2003.
[109]
J. M. Luque, J. Morante-Oria, and A. Fairén, “Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development,” Developmental Brain Research, vol. 140, no. 2, pp. 195–203, 2003.
[110]
E. Hartfuss, E. F？rster, H. H. Bock et al., “Reelin signaling directly affects radial glia morphology and biochemical maturation,” Development, vol. 130, pp. 4597–4609, 2003.
[111]
K. Sanada, A. Gupta, and L.-H. Tsai, “Disabled-1-regulated adhesion of migrating neurons to radial glial fiber contributes to neuronal positioning during early corticogenesis,” Neuron, vol. 42, no. 2, pp. 197–211, 2004.
[112]
R. M. Hoffarth, J. G. Johnston, L. A. Krushel, and D. Van der Kooy, “The mouse mutation reeler causes increased adhesion within a subpopulation of early postmitotic cortical neurons,” Journal of Neuroscience, vol. 15, no. 7, pp. 4838–4850, 1995.
[113]
S. J. Franco, I. Martinez-Garay, C. Gil-Sanz, S. R. Harkins-Perry, and U. Müller, “Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex,” Neuron, vol. 69, no. 3, pp. 482–497, 2011.
[114]
H. Tabata and K. Nakajima, “Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex,” Neuroscience, vol. 103, no. 4, pp. 865–872, 2001.
[115]
T. Miyata, Y. Ono, M. Okamoto et al., “Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum,” Neural Development, vol. 5, no. 1, article 23, 2010.
[116]
R. S. O'Dell, C. J. Ustine, D. A. Cameron et al., “Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone,” Neural Development, vol. 7, p. 25, 2012.
[117]
K. Sekine, T. Kawauchi, K. Kubo et al., “Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin α5β1,” Neuron, vol. 76, pp. 353–369, 2012.
[118]
C. Gil-Sanz, S. J. Franco, I. Martinez-Garay, A. Espinosa, S. Harkins-Perry, and U. Muller, “Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues,” Neuron, vol. 79, pp. 461–477, 2013.
[119]
Y. Jossin and J. A. Cooper, “Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex,” Nature Neuroscience, vol. 14, no. 6, pp. 697–703, 2011.
[120]
B. A. Ballif, L. Arnaud, and J. A. Cooper, “Tyrosine phosphorylation of disabled-1 is essential for Reelin-stimulated activation of Akt and Src family kinases,” Molecular Brain Research, vol. 117, no. 2, pp. 152–159, 2003.
[121]
U. Beffert, G. Morfini, H. H. Bock, H. Reyna, S. T. Brady, and J. Herz, “Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3β,” Journal of Biological Chemistry, vol. 277, no. 51, pp. 49958–49964, 2002.
[122]
H. H. Bock, Y. Jossin, P. Liu et al., “Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to reelin signaling and is required for normal cortical lamination,” Journal of Biological Chemistry, vol. 278, no. 40, pp. 38772–38779, 2003.
[123]
M. Laplante and D. M. Sabatini, “mTOR signaling at a glance,” Journal of Cell Science, vol. 122, no. 20, pp. 3589–3594, 2009.
[124]
D. D. Sarbassov, D. A. Guertin, S. M. Ali, and D. M. Sabatini, “Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex,” Science, vol. 307, no. 5712, pp. 1098–1101, 2005.
[125]
T. M. Kazdoba, C. N. Sunnen, B. Crowell, G. H. Lee, A. E. Anderson, and G. D'Arcangelo, “Development and characterization of NEX-Pten, a novel forebrain excitatory neuron-specific knockout mouse,” Developmental Neuroscience, vol. 34, no. 2-3, pp. 198–209, 2012.
[126]
C. B. Chan, X. Liu, S. Pradoldej et al., “Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex,” Journal of Neuroscience, vol. 31, no. 22, pp. 8083–8092, 2011.
[127]
J. Iafrati, M. J. Orejarena, O. Lassalle, L. Bouamrane, and P. Chavis, “Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway,” Molecular Psychiatry, 2013.
[128]
J. Trotter, G. H. Lee, T. M. Kazdoba et al., “Dab1 is required for synaptic plasticity and associative learning,” The Journal of Neuroscience, vol. 33, pp. 15652–15668, 2013.
[129]
S. Hirotsune, M. W. Fleck, M. J. Gambello et al., “Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality,” Nature Genetics, vol. 19, no. 4, pp. 333–339, 1998.
[130]
M. Hattori, H. Adachi, M. Tsujimoto, H. Arai, and K. Inoue, “Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor,” Nature, vol. 370, no. 6486, pp. 216–218, 1994.
[131]
O. Reiner, R. Carrozzo, Y. Shen et al., “Isolation of a Miller-Dieker lissencephaly gene containing G protein β-subunit-like repeats,” Nature, vol. 364, no. 6439, pp. 717–721, 1993.
[132]
A. H. Assadi, G. Zhang, U. Beffert et al., “Interaction of reelin signaling and Lis1 in brain development,” Nature Genetics, vol. 35, no. 3, pp. 270–276, 2003.
[133]
A. H. Assadi, G. Zhang, R. McNeil, G. D. Clark, and G. D'Arcangelo, “Pafah1b2 mutations suppress the development of hydrocephalus in compound Pafah1b1; Reln and Pafah1b1; Dab1 mutant mice,” Neuroscience Letters, vol. 439, no. 1, pp. 100–105, 2008.
[134]
G. Zhang, A. H. Assadi, M. Roceri, G. D. Clark, and G. D'Arcangelo, “Differential interaction of the Pafah1b alpha subunits with the Reelin transducer Dab1,” Brain Research, vol. 1267, pp. 1–8, 2009.
[135]
L.-H. Tsai and J. G. Gleeson, “Nucleokinesis in neuronal migration,” Neuron, vol. 46, no. 3, pp. 383–388, 2005.
[136]
A. Pramatarova, P. G. Ochalski, K. Chen et al., “Nckβ interacts with tyrosine-phosphorylated disabled 1 and redistributes in Reelin-stimulated neurons,” Molecular and Cellular Biology, vol. 23, no. 20, pp. 7210–7221, 2003.
[137]
R. Homayouni, S. Magdaleno, L. Keshvara, D. S. Rice, and T. Curran, “Interaction of disabled-1 and the GTPase activating protein Dab2IP in mouse brain,” Molecular Brain Research, vol. 115, no. 2, pp. 121–129, 2003.
[138]
Y. Huang, S. Magdaleno, R. Hopkins, C. Slaughter, T. Curran, and L. Keshvara, “Tyrosine phosphorylated disabled 1 recruits Crk family adapter proteins,” Biochemical and Biophysical Research Communications, vol. 318, no. 1, pp. 204–212, 2004.
[139]
G. H. Lee, S. H. Kim, R. Homayouni, and G. D'Arcangelo, “Dab2ip regulates neuronal migration and neurite outgrowth in the developing neocortex,” PLoS ONE, vol. 7, Article ID e46592, 2012.
[140]
S. Qiao, S. H. Kim, D. Heck, D. Goldowitz, M. S. LeDoux, and R. Homayouni, “Dab2IP GTPase activating protein regulates dendrite development and synapse number in cerebellum,” PLoS ONE, vol. 8, Article ID e53635, 2013.
[141]
T.-J. Park and T. Curran, “Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the reelin pathway,” Journal of Neuroscience, vol. 28, no. 50, pp. 13551–13562, 2008.
[142]
T. Hiesberger, M. Trommsdorff, B. W. Howell et al., “Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation,” Neuron, vol. 24, no. 2, pp. 481–489, 1999.
[143]
J. Herz, “The LDL receptor gene family: (Un)expected signal transducers in the brain,” Neuron, vol. 29, no. 3, pp. 571–581, 2001.
[144]
D. Benhayon, S. Magdaleno, and T. Curran, “Binding of purified Reelin to ApoER2 and VLDLR mediates tyrosine phosphorylation of disabled-1,” Molecular Brain Research, vol. 112, no. 1-2, pp. 33–45, 2003.
[145]
M. Trommsdorff, J.-P. Borg, B. Margolis, and J. Herz, “Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein,” Journal of Biological Chemistry, vol. 273, no. 50, pp. 33556–33560, 1998.
[146]
T. Morimura, M. Hattori, M. Ogawa, and K. Mikoshiba, “Disabled1 regulates the intracellular trafficking of reelin receptors,” Journal of Biological Chemistry, vol. 280, no. 17, pp. 16901–16908, 2005.
[147]
V. Strasser, D. Fasching, C. Hauser et al., “Receptor clustering is involved in Reelin signaling,” Molecular and Cellular Biology, vol. 24, no. 3, pp. 1378–1386, 2004.
[148]
G. Zhang, A. H. Assadi, R. S. McNeil et al., “The Pafah1b complex interacts with the reelin receptor VLDLR,” PLoS ONE, vol. 2, no. 2, article e252, 2007.
[149]
U. Beffert, E. J. Weeber, A. Durudas et al., “Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2,” Neuron, vol. 47, no. 4, pp. 567–579, 2005.
[150]
L. Dulabon, E. C. Olson, M. G. Taglienti et al., “Reelin binds α3β1 integrin and inhibits neuronal migration,” Neuron, vol. 27, no. 1, pp. 33–44, 2000.
[151]
D. Graus-Porta, S. Blaess, M. Senften et al., “β1-Class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex,” Neuron, vol. 31, no. 3, pp. 367–379, 2001.
[152]
R. Belvindrah, D. Graus-Porta, S. Goebbels, K.-A. Nave, and U. Müller, “β1 integrins in radial glia but not in migrating neurons are essential for the formation of cell layers in the cerebral cortex,” Journal of Neuroscience, vol. 27, no. 50, pp. 13854–13865, 2007.
[153]
E. F？rster, A. Tielsch, B. Saum et al., “Reelin, disabled 1, and β1 integrins are required for the formation of the radial glial scaffold in the hippocampus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 20, pp. 13178–13183, 2002.
[154]
K. Senzaki, M. Ogawa, and T. Yagi, “Proteins of the CNR family are multiple receptors for reelin,” Cell, vol. 99, no. 6, pp. 635–647, 1999.
[155]
A. Sentürk, S. Pfennig, A. Weiss, K. Burk, and A. Acker-Palmer, “Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration,” Nature, vol. 472, no. 7343, pp. 356–360, 2011.
[156]
T. Catchpole and M. Henkemeyer, “EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche,” Journal of Neuroscience, vol. 31, no. 32, pp. 11472–11483, 2011.
[157]
E. Bouche, M. I. Romero-Ortega, M. Henkemeyer et al., “Reelin induces EphB activation,” Cell Research, vol. 23, pp. 473–490, 2013.
[158]
V. Villar-Cervino, M. Molano-Mazon, T. Catchpole et al., “Contact repulsion controls the dispersion and final distribution of Cajal-Retzius cells,” Neuron, vol. 77, pp. 457–471, 2013.
[159]
T. Matsuki, A. Pramatarova, and B. W. Howell, “Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis,” Journal of Cell Science, vol. 121, no. 11, pp. 1869–1875, 2008.
[160]
C. Stritt and B. Kn？ll, “Serum response factor regulates hippocampal lamination and dendrite development and is connected with reelin signaling,” Molecular and Cellular Biology, vol. 30, no. 7, pp. 1828–1837, 2010.
[161]
J. Leemhuis and H. H. Bock, “Reelin modulates cytoskeletal organization by regulating Rho GTPases,” Communicative and Integrative Biology, vol. 4, no. 3, pp. 254–257, 2011.
[162]
M. Meseke, G. Rosenberger, and E. Forster, “Reelin and the Cdc42/Rac1 guanine nucleotide exchange factor alphaPIX/Arhgef6 promote dendritic Golgi translocation in hippocampal neurons,” European Journal of Neuroscience, vol. 37, pp. 1404–1412, 2013.
[163]
P. Chameau, D. Inta, T. Vitalis, H. Monyer, W. J. Wadman, and J. A. van Hooft, “The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 17, pp. 7227–7232, 2009.
[164]
H.-S. Hoe, J. L. Kea, R. S. E. Carney et al., “Interaction of Reelin with amyloid precursor protein promotes neurite outgrowth,” Journal of Neuroscience, vol. 29, no. 23, pp. 7459–7473, 2009.
[165]
H.-S. Hoe, T. S. Tran, Y. Matsuoka, B. W. Howell, and G. W. Rebeck, “DAB1 and reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing,” Journal of Biological Chemistry, vol. 281, no. 46, pp. 35176–35185, 2006.
[166]
J. H. Trotter, M. Klein, U. K. Jinwal et al., “ApoER2 function in the establishment and maintenance of retinal synaptic connectivity,” Journal of Neuroscience, vol. 31, no. 40, pp. 14413–14423, 2011.
[167]
S. Qiu, K. M. Korwek, A. R. Pratt-Davis, M. Peters, M. Y. Bergman, and E. J. Weeber, “Cognitive disruption and altered hippocampus synaptic function in Reelin haploinsufficient mice,” Neurobiology of Learning and Memory, vol. 85, no. 3, pp. 228–242, 2006.
[168]
P. Tueting, E. Costa, Y. Dwivedi et al., “The phenotypic characteristics of heterozygous reeler mouse,” NeuroReport, vol. 10, no. 6, pp. 1329–1334, 1999.
[169]
E. Costa, Y. Chen, J. Davis et al., “REELIN and schizophrenia: a disease at the interface of the genome and the epigenome,” Molecular Interventions, vol. 2, no. 1, pp. 47–57, 2002.
[170]
D. D. Krueger, J. L. Howell, B. F. Hebert, P. Olausson, J. R. Taylor, and A. C. Nairn, “Assessment of cognitive function in the heterozygous reeler mouse,” Psychopharmacology, vol. 189, no. 1, pp. 95–104, 2006.
[171]
W. S. Liu, C. Pesold, M. A. Rodriguez et al., “Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 6, pp. 3477–3482, 2001.
[172]
J. T. Rogers, L. Zhao, J. H. Trotter, et al., “Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse,” Journal of Psychopharmacology, vol. 27, pp. 386–395, 2013.
[173]
J. T. Rogers, I. Rusiana, J. Trotter et al., “Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density,” Learning and Memory, vol. 18, no. 9, pp. 558–564, 2011.
[174]
M. A. Rodriguez, C. Pesold, W. S. Liu et al., “Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3550–3555, 2000.
[175]
L. A. Glantz and D. A. Lewis, “Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia,” Archives of General Psychiatry, vol. 57, no. 1, pp. 65–73, 2000.
[176]
J. L. Brigman, K. E. Padukiewicz, M. L. Sutherland, and L. A. Rothblat, “Executive functions in the heterozygous reeler mouse model of schizophrenia,” Behavioral Neuroscience, vol. 120, no. 4, pp. 984–988, 2006.
[177]
A. M. Barr, K. N. Fish, A. Markou, and W. G. Honer, “Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins,” European Journal of Neuroscience, vol. 27, no. 10, pp. 2568–2574, 2008.
[178]
V. Martínez-Cerde？o, M. J. Galazo, C. Cavada, and F. Clasca, “Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions,” Cerebral Cortex, vol. 12, no. 12, pp. 1298–1311, 2002.
[179]
C. Pesold, W. S. Liu, A. Guidotti, E. Costa, and H. J. Caruncho, “Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 6, pp. 3217–3222, 1999.
[180]
R. C. Roberts, L. Xu, J. K. Roche, and B. Kirkpatrick, “Ultrastructural localization of reelin in the cortex in post-mortem human brain,” Journal of Comparative Neurology, vol. 482, no. 3, pp. 294–308, 2005.
[181]
E. J. Weeber, U. Beffert, C. Jones et al., “Reelin and apoE receptors cooperate to enhance hippocampal synaptic plasticity and learning,” Journal of Biological Chemistry, vol. 277, no. 42, pp. 39944–39952, 2002.
[182]
C. G. Campo, M. Sinagra, D. Verrier, O. J. Manzoni, and P. Chavis, “Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis,” PloS ONE, vol. 4, no. 5, Article ID e5505, 2009.
[183]
Y. Chen, U. Beffert, M. Ertunc et al., “Reelin modulates NMDA receptor activity in cortical neurons,” Journal of Neuroscience, vol. 25, no. 36, pp. 8209–8216, 2005.
[184]
L. Groc, D. Choquet, F. A. Stephenson, D. Verrier, O. J. Manzoni, and P. Chavis, “NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein reelin,” Journal of Neuroscience, vol. 27, no. 38, pp. 10165–10175, 2007.
[185]
S. Qiu and E. J. Weeber, “Reelin signaling facilitates maturation of CA1 glutamatergic synapses,” Journal of Neurophysiology, vol. 97, no. 3, pp. 2312–2321, 2007.
[186]
S. Qiu, L. F. Zhao, K. M. Korwek, and E. J. Weeber, “Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus,” Journal of Neuroscience, vol. 26, no. 50, pp. 12943–12955, 2006.
[187]
S. Hellwig, I. Hack, J. Kowalski et al., “Role for reelin in neurotransmitter release,” Journal of Neuroscience, vol. 31, no. 7, pp. 2352–2360, 2011.
[188]
I. Knuesel, “Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases,” Progress in Neurobiology, vol. 91, no. 4, pp. 257–274, 2010.
