Gene Symbol: Reln
Description: reelin
Alias: reeler, reelin, extracellular matrix serine protease
Species: mouse
Products:     Reln

Top Publications

  1. Sharaf A, Bock H, Spittau B, Bouché E, Krieglstein K. ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal migration and positioning of mesencephalic dopaminergic neurons. PLoS ONE. 2013;8:e71091 pubmed publisher
    ..b>Reelin and the cytoplasmic adaptor protein Disabled-1 (Dab1) have been shown to play important roles in the migration and ..
  2. Jossin Y, Cooper J. Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex. Nat Neurosci. 2011;14:697-703 pubmed publisher
    ..Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipolar neurons to polarize their migration toward the ..
  3. Qiu S, Zhao L, Korwek K, Weeber E. Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. J Neurosci. 2006;26:12943-55 pubmed
    ..lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor)...
  4. Nomura T, Takahashi M, Hara Y, Osumi N. Patterns of neurogenesis and amplitude of Reelin expression are essential for making a mammalian-type cortex. PLoS ONE. 2008;3:e1454 pubmed publisher
    ..Furthermore, expression of Reelin gene is hardly detected in the developing avian pallium, and an experimental increase in Reelin-positive cells in ..
  5. Inoue T, Ogawa M, Mikoshiba K, Aruga J. Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly. J Neurosci. 2008;28:4712-25 pubmed publisher
    ..These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly. ..
  6. Simo S, Jossin Y, Cooper J. Cullin 5 regulates cortical layering by modulating the speed and duration of Dab1-dependent neuronal migration. J Neurosci. 2010;30:5668-76 pubmed publisher
    ..Correct layering requires an extracellular protein, Reelin (Reln), an intracellular signaling molecule, Disabled-1 (Dab1), and an E3 ubiquitin ligase, Cullin-5 (Cul5)...
  7. Pla R, Borrell V, Flames N, Marin O. Layer acquisition by cortical GABAergic interneurons is independent of Reelin signaling. J Neurosci. 2006;26:6924-34 pubmed
    ..The radial migration and laminar arrangement of projection neurons depends on Reelin, a secreted glycoprotein expressed near the pial surface during embryogenesis...
  8. Ammassari Teule M, Sgobio C, Biamonte F, Marrone C, Mercuri N, Keller F. Reelin haploinsufficiency reduces the density of PV+ neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors. Psychopharmacology (Berl). 2009;204:511-21 pubmed publisher
    ..extracellular matrix glycoprotein, is down-regulated in the brain of schizophrenic patients and of heterozygous reeler mice (rl/+). The behavioral phenotype of rl/- mice, however, matches only partially the schizophrenia hallmarks...
  9. Miyata T, Ono Y, Okamoto M, Masaoka M, Sakakibara A, Kawaguchi A, et al. Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum. Neural Dev. 2010;5:23 pubmed publisher
    ..In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly ..

More Information


  1. Matsuki T, Matthews R, Cooper J, van der Brug M, Cookson M, Hardy J, et al. Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment. Cell. 2010;143:826-36 pubmed publisher
    The Reelin ligand regulates a Dab1-dependent signaling pathway required for brain lamination and normal dendritogenesis, but the specific mechanisms underlying these actions remain unclear...
  2. Kohno S, Kohno T, Nakano Y, Suzuki K, Ishii M, Tagami H, et al. Mechanism and significance of specific proteolytic cleavage of Reelin. Biochem Biophys Res Commun. 2009;380:93-7 pubmed publisher
    b>Reelin is a secreted glycoprotein essential for normal brain development and function. In the extracellular milieu, Reelin is subject to specific cleavage at two (N-t and C-t) sites...
  3. Boyle M, Bernard A, Thompson C, Ng L, Boe A, Mortrud M, et al. Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala. J Comp Neurol. 2011;519:2061-89 pubmed publisher
    The disrupted cortical lamination phenotype in reeler mice and subsequent identification of the Reelin signaling pathway have strongly informed models of cortical development...
  4. Niu S, Renfro A, Quattrocchi C, Sheldon M, D ARCANGELO G. Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway. Neuron. 2004;41:71-84 pubmed
    ..In addition to cellular disorganization, dendrite abnormalities are present in the brain of reeler mice lacking Reelin...
  5. Zhao S, Chai X, Forster E, Frotscher M. Reelin is a positional signal for the lamination of dentate granule cells. Development. 2004;131:5117-25 pubmed
    b>Reelin is required for the proper positioning of neurons in the cerebral cortex. In the reeler mutant lacking reelin, the granule cells of the dentate gyrus fail to form a regular, densely packed cell layer...
  6. Shen Q, Wang Y, Dimos J, Fasano C, Phoenix T, Lemischka I, et al. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nat Neurosci. 2006;9:743-51 pubmed
    ..Our data demonstrate that neural stem cells change neuropotency during development and have a window of plasticity when restrictions can be reversed. ..
  7. Nishikawa S, Goto S, Yamada K, Hamasaki T, Ushio Y. Lack of Reelin causes malpositioning of nigral dopaminergic neurons: evidence from comparison of normal and Reln(rl) mutant mice. J Comp Neurol. 2003;461:166-73 pubmed
    The reeler gene (Reln(rl), formerly rl) product Reelin controls neuronal migration and positioning and thereby plays a key role in brain development...
  8. Barber M, di Meglio T, Andrews W, Hernández Miranda L, Murakami F, Chedotal A, et al. The role of Robo3 in the development of cortical interneurons. Cereb Cortex. 2009;19 Suppl 1:i22-31 pubmed publisher
    ..These observations and the results of other recent studies suggest a complex interplay between the 3 Robo receptors in regulating the number, migration and morphological differentiation of cortical interneurons. ..
  9. Matsuki T, Pramatarova A, Howell B. Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis. J Cell Sci. 2008;121:1869-75 pubmed publisher
    The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis...
  10. Bodea G, Spille J, Abe P, Andersson A, Acker Palmer A, Stumm R, et al. Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system. Development. 2014;141:661-73 pubmed publisher
    ..We show that tangentially migrating dopaminergic neurons express the components of the reelin signaling pathway, whereas dopaminergic neurons in their initial, radial migration phase express CXC chemokine ..
  11. Nieto M, Monuki E, Tang H, Imitola J, Haubst N, Khoury S, et al. Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV of the cerebral cortex. J Comp Neurol. 2004;479:168-80 pubmed
    ..The patterns of expression of Cux genes suggest potential roles as determinants of the neuronal fate of the upper cortical layer neurons. ..
  12. Zhao S, Chai X, Bock H, Brunne B, Forster E, Frotscher M. Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for Reelin and Disabled 1. J Comp Neurol. 2006;495:1-9 pubmed
    Reelin is a positional signal for the lamination of the dentate gyrus. In the reeler mutant lacking Reelin, granule cells are scattered all over the dentate gyrus...
  13. Zhao S, Chai X, Frotscher M. Balance between neurogenesis and gliogenesis in the adult hippocampus: role for reelin. Dev Neurosci. 2007;29:84-90 pubmed
    The extracellular matrix protein reelin is essential for the proper radial migration of cortical neurons. In reeler mice lacking reelin, there is a malformation of the radial glial scaffold required for granule cell migration...
  14. Yip Y, Mehta N, Magdaleno S, Curran T, Yip J. Ectopic expression of reelin alters migration of sympathetic preganglionic neurons in the spinal cord. J Comp Neurol. 2009;515:260-8 pubmed publisher
    ..In reeler, which lacks Reelin, SPN also undergo primary migration to the ventrolateral spinal cord as in wildtype...
  15. Kocherhans S, Madhusudan A, Doehner J, Breu K, Nitsch R, Fritschy J, et al. Reduced Reelin expression accelerates amyloid-beta plaque formation and tau pathology in transgenic Alzheimer's disease mice. J Neurosci. 2010;30:9228-40 pubmed publisher
    ..role of Reelin in amyloid-beta plaque and Tau pathology in vivo, we crossed heterozygous Reelin knock-out mice (reeler) with transgenic AD mice to investigate the temporal and spatial AD-like neuropathology...
  16. Martín López E, Blanchart A, De Carlos J, López Mascaraque L. Dab1 (Disable homolog-1) reelin adaptor protein is overexpressed in the olfactory bulb at early postnatal stages. PLoS ONE. 2011;6:e26673 pubmed publisher
    Dab1 mediates reelin signalling and plays critical roles in early brain development such as the stereotypical positioning of neurons in the brain...
  17. Niu S, Yabut O, D ARCANGELO G. The Reelin signaling pathway promotes dendritic spine development in hippocampal neurons. J Neurosci. 2008;28:10339-48 pubmed publisher
    ..The extracellular protein Reelin, through the activation of a core signaling pathway, including the receptors ApoER2 and VLDLR (very low density ..
  18. Won S, Kim S, Xie L, Wang Y, Mao X, Jin K, et al. Reelin-deficient mice show impaired neurogenesis and increased stroke size. Exp Neurol. 2006;198:250-9 pubmed
    b>Reelin (Reln) is a protein involved in migration of newborn neurons during development...
  19. Englund C, Fink A, Lau C, Pham D, Daza R, Bulfone A, et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci. 2005;25:247-51 pubmed
  20. Schneider S, Gulacsi A, Hatten M. Lrp12/Mig13a reveals changing patterns of preplate neuronal polarity during corticogenesis that are absent in reeler mutant mice. Cereb Cortex. 2011;21:134-44 pubmed publisher
    ..These changes in neuronal polarity do not occur in reeler mutant mice, revealing the earliest known defect in reeler cortical patterning and suggesting that the alignment ..
  21. Perez Garcia C, Tissir F, Goffinet A, Meyer G. Reelin receptors in developing laminated brain structures of mouse and human. Eur J Neurosci. 2004;20:2827-32 pubmed
    b>Reelin is an extracellular matrix protein secreted by a variety of cell types throughout the developing brain. The target cells for reelin express the cytoplasmic adapter protein Dab1, which binds to the reelin receptors VLDLR and ApoER2...
  22. Arnaud L, Ballif B, Cooper J. Regulation of protein tyrosine kinase signaling by substrate degradation during brain development. Mol Cell Biol. 2003;23:9293-302 pubmed
    ..Dab1 function in vivo depends on tyrosine phosphorylation, which is stimulated by extracellular Reelin and requires Src family kinases...
  23. Ognibene E, Adriani W, Granstrem O, Pieretti S, Laviola G. Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice. Brain Res. 2007;1131:173-80 pubmed
    b>Reelin is an extracellular matrix protein, secreted by GABAergic interneurons, that provides a signal for neural plasticity. A downregulation of reelin may be a factor to be considered in the study of major psychiatric disorders...
  24. Qiu S, Weeber E. Reelin signaling facilitates maturation of CA1 glutamatergic synapses. J Neurophysiol. 2007;97:2312-21 pubmed
    ..In cultured hippocampal neurons from reeler embryos, reduced numbers of AMPAR subunit GluR1 and NMDAR subunit NR1 clustering were observed compared with those ..
  25. Cabrera Socorro A, Hernandez Acosta N, Gonzalez Gomez M, Meyer G. Comparative aspects of p73 and Reelin expression in Cajal-Retzius cells and the cortical hem in lizard, mouse and human. Brain Res. 2007;1132:59-70 pubmed
    Cajal-Retzius (CR) cells of the mammalian neocortex co-express the extracellular matrix protein Reelin and p73, a transcription factor involved in cell death and survival...
  26. Villeda S, Akopians A, Babayan A, Basbaum A, Phelps P. Absence of Reelin results in altered nociception and aberrant neuronal positioning in the dorsal spinal cord. Neuroscience. 2006;139:1385-96 pubmed
    Mutations in reeler, the gene coding for the Reelin protein, result in pronounced motor deficits associated with positioning errors (i.e. ectopic locations) in the cerebral and cerebellar cortices...
  27. Sibbe M, Forster E, Basak O, Taylor V, Frotscher M. Reelin and Notch1 cooperate in the development of the dentate gyrus. J Neurosci. 2009;29:8578-85 pubmed publisher
    ..In Reelin-deficient Reeler mice, the hippocampal radial glial scaffold fails to form, and granule cells are dispersed throughout the dentate ..
  28. Hammond V, So E, Gunnersen J, Valcanis H, Kalloniatis M, Tan S. Layer positioning of late-born cortical interneurons is dependent on Reelin but not p35 signaling. J Neurosci. 2006;26:1646-55 pubmed
    We tested the response of interneurons to the absence of Reelin signaling or p35 in the mouse neocortex...
  29. Hoareau C, Borrell V, Soriano E, Krebs M, Prochiantz A, Allinquant B. Amyloid precursor protein cytoplasmic domain antagonizes reelin neurite outgrowth inhibition of hippocampal neurons. Neurobiol Aging. 2008;29:542-53 pubmed
    ..with the APP cytoplasmic domain in vitro and in heterologous systems is Disabled-1, a signaling molecule of the reelin pathway. The physiological consequence of this interaction is unknown...
  30. MacLaurin S, Krucker T, Fish K. Hippocampal dendritic arbor growth in vitro: regulation by Reelin-Disabled-1 signaling. Brain Res. 2007;1172:1-9 pubmed
    The cytoplasmic adaptor protein Disabled-1 (Dab1), which is a key component of the Reelin-signaling pathway, has been suggested to be required for neuronal dendritic development...
  31. Tissir F, Ravni A, Achouri Y, Riethmacher D, Meyer G, Goffinet A. DeltaNp73 regulates neuronal survival in vivo. Proc Natl Acad Sci U S A. 2009;106:16871-6 pubmed publisher
    ..However, ablation of cells that express DeltaNp73 and Wnt3a did neither remove all CRc, nor did they abolish Reelin secretion or generate a reeler-like cortical phenotype...
  32. Trotter J, Klein M, Jinwal U, Abisambra J, Dickey C, Tharkur J, et al. ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. J Neurosci. 2011;31:14413-23 pubmed publisher
    ..b>Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and ..
  33. Goebbels S, Bormuth I, Bode U, Hermanson O, Schwab M, Nave K. Genetic targeting of principal neurons in neocortex and hippocampus of NEX-Cre mice. Genesis. 2006;44:611-21 pubmed
    ..The NEX-Cre mouse will be a valuable tool for behavioral research and the conditional inactivation of target genes in pyramidal neurons of the dorsal telencephalon. ..
  34. Harrison S, Parrish M, Monaghan A. Sall3 is required for the terminal maturation of olfactory glomerular interneurons. J Comp Neurol. 2008;507:1780-94 pubmed publisher
    ..Our data suggest that Sall3 is required for the terminal maturation of neurons destined for the glomerular layer. ..
  35. Borrell V, Pujadas L, Simo S, Durà D, Solé M, Cooper J, et al. Reelin and mDab1 regulate the development of hippocampal connections. Mol Cell Neurosci. 2007;36:158-73 pubmed
    ..severe alterations in the entorhino-hippocampal and commissural connections identical to those described in reeler mice, including innervation of ectopic areas, formation of abnormal patches of fiber termination and a delay in ..
  36. Yamamoto T, Sakakibara S, Mikoshiba K, Terashima T. Ectopic corticospinal tract and corticothalamic tract neurons in the cerebral cortex of yotari and reeler mice. J Comp Neurol. 2003;461:61-75 pubmed
    Reeler and yotari mice, which are mutant for Reelin or Dab1, respectively, show disorders of cerebral cortical lamination...
  37. Stumm R, Zhou C, Ara T, Lazarini F, Dubois Dalcq M, Nagasawa T, et al. CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci. 2003;23:5123-30 pubmed
    ..Thus, our findings suggest that SDF-1, which is highly expressed in the embryonic leptomeninx, selectively regulates migration and layer-specific integration of CXCR4-expressing interneurons during neocortical development. ..
  38. Morimura T, Hattori M, Ogawa M, Mikoshiba K. Disabled1 regulates the intracellular trafficking of reelin receptors. J Biol Chem. 2005;280:16901-8 pubmed
    b>Reelin is a huge secreted protein that controls proper laminar formation in the developing brain...
  39. Wang Y, Li G, Stanco A, Long J, Crawford D, Potter G, et al. CXCR4 and CXCR7 have distinct functions in regulating interneuron migration. Neuron. 2011;69:61-76 pubmed publisher
    ..On the other hand, CXCL12 stimulation of CXCR7, but not CXCR4, promoted MAP kinase signaling. Thus, we suggest that CXCR4 and CXCR7 have distinct roles and signal transduction in regulating interneuron movement and laminar positioning. ..
  40. Lai T, Jabaudon D, Molyneaux B, Azim E, Arlotta P, Menezes J, et al. SOX5 controls the sequential generation of distinct corticofugal neuron subtypes. Neuron. 2008;57:232-47 pubmed publisher
    ..These data indicate that SOX5 controls the timing of critical fate decisions during corticofugal neuron production and thus subtype-specific differentiation and neocortical neuron diversity. ..
  41. Panteri R, Mey J, Zhelyaznik N, D Altocolle A, Del Fa A, Gangitano C, et al. Reelin is transiently expressed in the peripheral nerve during development and is upregulated following nerve crush. Mol Cell Neurosci. 2006;32:133-42 pubmed
    b>Reelin is an extracellular matrix protein which is critical for the positioning of migrating post-mitotic neurons and the laminar organization of several brain structures during development...
  42. Jossin Y, Goffinet A. Reelin signals through phosphatidylinositol 3-kinase and Akt to control cortical development and through mTor to regulate dendritic growth. Mol Cell Biol. 2007;27:7113-24 pubmed
    b>Reelin is an extracellular matrix protein with various functions during development and in the mature brain...
  43. Ballif B, Arnaud L, Arthur W, Guris D, Imamoto A, Cooper J. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol. 2004;14:606-10 pubmed
    ..secreted protein Reelin controls the locations of many types of neurons, and its absence causes the classic "Reeler" phenotype...
  44. Krueger D, Howell J, Hebert B, Olausson P, Taylor J, Nairn A. Assessment of cognitive function in the heterozygous reeler mouse. Psychopharmacology (Berl). 2006;189:95-104 pubmed
    ..However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent ..
  45. Sekine K, Kawauchi T, Kubo K, Honda T, Herz J, Hattori M, et al. Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin ?5?1. Neuron. 2012;76:353-69 pubmed publisher
    Birthdate-dependent neuronal layering is fundamental to neocortical functions. The extracellular protein Reelin is essential for the establishment of the eventual neuronal alignments...
  46. Pujadas L, Gruart A, Bosch C, Delgado L, Teixeira C, Rossi D, et al. Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long-term potentiation. J Neurosci. 2010;30:4636-49 pubmed publisher
    b>Reelin, an extracellular protein essential for neural migration and lamination, is also expressed in the adult brain...
  47. Harrison S, Nishinakamura R, Monaghan A. Sall1 regulates mitral cell development and olfactory nerve extension in the developing olfactory bulb. Cereb Cortex. 2008;18:1604-17 pubmed
    ..In Sall1-mutant animals, these patterns of neurogenesis were disrupted. These findings suggest a role for Sall1 in regulating neuronal differentiation and maturation in developing neural structures. ..
  48. Hanashima C, Fernandes M, Hebert J, Fishell G. The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J Neurosci. 2007;27:11103-11 pubmed
  49. Morimura T, Ogawa M. Relative importance of the tyrosine phosphorylation sites of Disabled-1 to the transmission of Reelin signaling. Brain Res. 2009;1304:26-37 pubmed publisher
    b>Reelin regulates radial migration of the projection neurons in the developing cerebral cortex by inducing tyrosine phosphorylation of an intracellular adaptor protein, Disabled-1 (Dab1), through activation of Src family tyrosine kinases (..
  50. Lopez Bendito G, Sánchez Alcañiz J, Pla R, Borrell V, Picó E, Valdeolmillos M, et al. Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons. J Neurosci. 2008;28:1613-24 pubmed publisher
  51. Yoshida M, Assimacopoulos S, Jones K, Grove E. Massive loss of Cajal-Retzius cells does not disrupt neocortical layer order. Development. 2006;133:537-45 pubmed
    Cajal-Retzius (CR) cells, the predominant source of reelin in developing neocortex, are thought to be essential for the inside out formation of neocortical layers...
  52. Yamashita N, Uchida Y, Ohshima T, Hirai S, Nakamura F, Taniguchi M, et al. Collapsin response mediator protein 1 mediates reelin signaling in cortical neuronal migration. J Neurosci. 2006;26:13357-62 pubmed
    ..Here, we show evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal migration in the cerebral cortex...
  53. Díaz Ruiz C, Parlato R, Aguado F, Ureña J, Burgaya F, MARTINEZ A, et al. Regulation of neural migration by the CREB/CREM transcription factors and altered Dab1 levels in CREB/CREM mutants. Mol Cell Neurosci. 2008;39:519-28 pubmed publisher