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At least 19 recordsLinked to original sources
PubMed1997

A truncated Reelin protein is produced but not secreted in the 'Orleans' reeler mutation (Reln[rl-Orl]).

Reelin is the protein defective in reeler mutant mice [I. Bar, C. Lambert de Rouvroit, I. Royaux, D.B. Krizman, C. Dernoncourt, D. Ruelle, M.C. Beckers, A.M. Goffinet, A YAC contig containing the reeler locus with preliminary characterization of candidate gene fragments, Genomics 26 (1995) 543-549; G. D'Arcangelo, G.G. Miao, S.C. Chen, H.D. Soares, J.I. Morgan, T. Curran, A protein related to extracellular matrix proteins deleted in the mouse mutant reeler, Nature 374 (1995) 719-723; S. Hirotsune, T. Takahara, N. Sasaki, K. Hirose, A. Yoshiki, T. Ohashi, M. Kusakabe, Y. Murakami, M. Muramatsu, S. Watanabe, K. Nakao, M. Katsuki, Y. Hayashizaki, The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons, Nature Genet. 10 (1995) 77-83]. In the Orleans allele of reeler (symbol: Reln[rl-Orl]), a 220 nucleotide deletion is present in the 3' region of the Reelin message, resulting in a frame shift with production of a predicted protein amputated from its C-terminal amino acids. In this study, we first show that the predicted truncated protein indeed exists in Orleans reeler mice, using several anti-Reelin antibodies. Three antibodies are directed against epitopes located in the N-terminal region of the protein, namely: monoclonal antibody CR-50 [M. Ogawa, T. Miyata, K. Nakajima, K. Yagyu, M. Seike, K. Ikenaka, H. Yamamoto, K. Mikoshiba, The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons, Neuron 14 (1995) 899-912] (epitope region between Reelin residues 251-407), monoclonal antibody G10 (epitope located between amino acids 199 and 244) and the polyclonal antipeptide rp4 (positions 381-399). A fourth antibody, antipeptide rp5, reacts with the C-terminal (3443-3461) Reelin sequence. In normal embryos, all four antibodies stained cells in the marginal zone with features of Cajal-Retzius cells. While N-terminal specific antibodies detected Reelin immunoreactivity in mouse embryos homozygous for the reeler-Orleans mutation, no staining was obtained with the rp5 antibody, showing the presence of a truncated protein. Moreover, although Reelin could be detected at the surface of living Cajal-Retzius cells of normal mice, it was not revealed after vital staining of embryonic cortex from Orleans reeler mice. These results indicate that the C-terminal region of Reelin is essential for its secretion and suggest that the Orleans reeler phenotype is due to defective Reelin secretion rather than to secretion of an inactive protein.

Amino Acid Sequence↗
PubMed1997

Birthdate and cell marker analysis of scrambler: a novel mutation affecting cortical development with a reeler-like phenotype.

The reeler mutation in mice produces an especially well characterized disorder, with systematically abnormal migration of cerebral cortical neurons. The reeler gene encodes a large protein, termed Reelin, that in the cortex is synthesized and secreted exclusively in the Cajal-Retzius neurons of the cortical marginal zone (D'Arcangelo et al., 1995). In reeler mutant mice, loss of Reelin protein is associated with a systematic loss of the normal, "inside-out" sequence of neurogenesis in the cortex: neurons are formed in the normal sequence but become localized in the cortex in a somewhat inverted, although relatively disorganized "outside-in" pattern. Here we show that the scrambler mutant mouse exhibits a loss of lamination in the cortex and hippocampus that is indistinguishable from that seen in the reeler mouse. We use BrdU birthdating studies to show that scrambler cortex shows a somewhat inverted "outside-in" sequence of birthdates for cortical neurons that is similar to that previously described in reeler cortex. Finally, we perform staining with the CR-50 monoclonal antibody (Ogawa et al., 1995), which recognizes the Reelin protein (D'Arcangelo et al., 1997). We show that Reelin immunoreactivity is present in the scrambler cortex in a normal pattern, suggesting that Reelin is synthesized and released normally. Our data suggest that scrambler is a mutation in the same gene pathway as the reeler gene (Relnrl) and is most likely downstream of Relnrl.

Animals↗
PubMed1998

Ambiguus nucleus neurons innervating the abdominal esophagus are malpositioned in the reeler mouse.

To examine whether the migration of ambiguus nucleus (NA) neurons is affected in the reeler mouse, recombinant replication-deficient adenoviral vector carrying E. coli-galactosidase gene (lacZ) was injected into the abdominal esophagus of the reeler mouse and normal control at two months of age prior to 5 days of sacrifice of the animals. In the normal control, lacZ-positive neurons were found in the compact formation of the NA, whereas, in the reeler, they were scattered from the base of the fourth ventricle to the ventro-lateral margin of the medulla. The present study confirmed that NA neurons are malpositioned in the reeler mouse, suggesting that the migration of NA neurons is guided by the reelin-related protein (Reelin).

Abdomen↗
PubMed1999

[Cytoarchitectonic abnormality in the facial nucleus of the reeler mouse].

Reeler, an autosomal recessive mutant mouse, is characterized by ataxic gait and tremor. In this mutant, the cerebral and cerebellar cortices and hippocampus are cytoarchitectually disorganized: neuronal components are ectopically located in these laminated structures. Since reelin, the gene responsible for the reeler mutation, was discovered by D'Arcangelo et al. (Nature 374: 719-723, 1995), remarkable progress has occurred in this field. The reelin gene encodes an extracellular protein, Reelin, that is crucial for neuronal migration. During embryogenesis, reelin is expressed in the Cajal-Retzius cells in the cerebral cortex and in the outer granule cells in the cerebellar cortex. Although non-laminated structures such as facial nucleus, inferior olivary complex, and dorsal cochlear nucleus are also cytoarchitectually deranged in this mutant, only a few studies have been done to clarify the detailed abnormalities in these non-laminated structures. In this review, we focused on the cytoarchitectonic abnormality in the facial nucleus of the reeler mouse. The branchiomotor neurons in the facial nucleus are generated from the ventricular zone of the floor of the fourth ventricle, migrate ventrolaterally, and finally settle near the ventral surface of the hindbrain. Time schedules for the generation, axon formation and migration of facial motoneurons are similar both in the normal and reeler mice, but the reeler phenotype becomes identifiable at the end of neuronal migration. Although the reason why the facial nucleus is cytoarchitectually abnormal in the reeler mouse is still unknown, the long migration of the facial motoneurons seems to be susceptible to the absence of Reelin in the reeler mouse. In spite of the cytoarchitectual abnormality, retrograde horseradish peroxidase (HRP) study confirmed that the musculotopic arrangements within the facial nucleus of the reeler mouse are still preserved, suggesting that neuronal migration and target recognition are regulated independently. More recently, other reeler-like mutants have been reported. Among them, yotari and scrambler mice arise from mutations in mdab1, a mouse gene related to Drosophila gene disabled (dab). More than 10 years ago, an autosomal recessive rat mutant, shaking rat Kawasaki (SRK), was described that exhibits a phenotype identical to reeler, but the gene responsible for this rat mutation remains unknown. Interestingly, the facial nucleus is cytoarchitectually more deranged in yotari and SRK than their reeler counterpart. Although the reason why yotari exhibits a phenotype identical to reeler in the laminated structures but not in non-laminated structures such as the facial nucleus has remained obscure, mDab1 and Reelin proteins may function as signaling molecules in a different way between laminated and non-laminated structures. Phenotypes resembling that of reeler are seen with mutations in mdab1, cdk5 and p35. Cdk5 and p35 are respectively the catalytic and regulatory subunits of a serine/threonine kinase, that could potentially operate in a common signalling pathway with mDab and Reelin. These plausible partners for Reelin and mDab1 should help us to understand how the activities of these proteins coordinate neuronal migration and rearrangement.

Animals↗
PubMed2001

Stereological estimates of total neuron numbers in the hippocampus of adult reeler mutant mice: Evidence for an increased survival of Cajal-Retzius cells.

The cytoarchitecture of the brain is disrupted severely in reeler mice. This is caused by a deficiency in the protein, Reelin, which is essential for the normal migration and positioning of neurons during development. Although cell migration is clearly affected by the reeler mutation, it is believed that the total number of neurons is not. Thus, we were surprised to find an unusually large number of calretinin-immunopositive cells, presumably Cajal-Retzius cells, in the molecular layer of the adult reeler hippocampus (Deller et al. [1999]; Exp. Neurol. 156:239-253). This suggested that the reeler mutation affects the number of neurons in the hippocampus. In order to verify this hypothesis, unbiased stereological methods were employed. Calretinin immunostaining was used as a marker for Cajal-Retzius cells in control as well as reeler mice and Nissl staining was used to identify hippocampal principal neurons. Total numbers of calretinin-immunopositive cells, calretinin-immunoreactive Cajal-Retzius cells, and Nissl-stained neurons were estimated in different subfields of the reeler and the control hippocampus. Stereological estimates (P < 0.05) revealed that the total number of calretinin-immunopositive and Cajal-Retzius cells in reeler mice are 1.5 and 2.1 times that of controls, respectively. No significant difference in total neuron number was found in any hippocampal subfield. These data demonstrate that the reeler mutation affects the number of calretinin-immunoreactive Cajal-Retzius cells in the adult hippocampus, probably due to a reduced excitatory innervation by entorhinal terminals in the absence of reelin. However, the reeler mutation does not affect mechanisms that determine total hippocampal neuron number.

Animals↗
PubMed1996

Extracellular matrix in early cortical development.

Studies of the distribution and production of ECM components during development of the cerebral cortex have suggested several hypotheses regarding their functional role. In the earliest stages of cortical development, fibronectin is produced by cells in the ventricular zone throughout the telencephalic vesicle, where it may serve as a part of the local environment that supports cell division and determines cell fate. Fibronectin is also distributed along radial glial processes. It is closely associated with preplate neurons, as are chondroitin sulfate proteoglycans and several other ECM components. This association continues as preplate cells are divided into the marginal zone and subplate by the invasion of cortical plate neurons, suggesting that ECM, preplate cells and radial glia serve as a scaffold for cortical plate formation. Fibronectin is also produced by migrating neurons, but only by those moving into specific cortical domains, suggesting that it may help neurons destined for specific targets discriminate between adjacent glial guides. A recently defined ECM-like protein, reelin, is absent or abnormal in the reeler mutant mouse in which cortical neurons are severely malpositioned. Reelin is produced by marginal zone cells and is therefore appropriately located to serve as a stop signal for migrating neurons. Axons leaving the cortical plate cross the CSPG-rich subplate, then turn to follow a path containing much less CSPG. In contrast, the cortical trajectory of thalamic axons is centered on the subplate, indicating that CSPGs in the subplate are not a barrier to axon outgrowth and may instead be serving as guidance cues that distinguish afferent from efferent pathways. Neurocan, a CNS-specific CSPG with many molecular features that indicate roles in cell-cell and cell-substrate interactions, is the only CSPG defined to date whose distribution supports a role in distinguishing afferent from efferent pathways.

Animals↗
PubMed1999

Transient and compartmental expression of the reeler gene product reelin in the developing rat striatum.

Mammalian neostriatum is composed of two neurochemically and neuroanatomically defined compartments, called the patches and matrix. The present study concerns a search for neurochemical molecules involved in formation of the striatal compartments. Using the monoclonal antibody CR-50, we here disclose a transient expression of the reeler gene product Reelin, which is known to play a crucial role in neuronal positioning and axon guidance during corticogenesis, in the developing striatum of rats. Furthermore, Reelin protein is differentially concentrated in the two distinct compartments showing a mosaic-like fashion in the early postnatal period: the compartments of heightened CR-50-immunolabeling correspond to so-called "dopamine islands" (i.e., developing striosomes) visualized by tyrosine hydroxylase (TH)-immunostaining. On the basis of these findings, we hypothesize that Reelin protein may play a role in developmental organization of the striatal compartments.

Animals↗
PubMed2000

The Reelin signaling pathway in mouse cortical development.

Most of the cerebral cortex derives from the cortical plate which, in all mammals, is radially organized and develops from inside to outside. Several genes involved in the organization and inside-outside development of the embryonic cortical plate in the mouse form the so-called Reelin signaling pathway. Biochemical and genetic arguments show that the extracellular matrix protein Reelin binds to two lipoprotein receptors (VLDLR and ApoER2), which relay the Reelin signal inside target neurons by docking the tyrosine kinase adapter disabled-1 (Dab1). In addition, biochemical evidence suggests that the integrins alpha 3/beta 1 and protocadherins of the CNR family may also modulate the Reelin signal. The mechanisms by which the presence of Reelin stops migration and instructs the radial organization of cortical plate cells remains unknown.

Animals↗
PubMed1999

Reelin is a ligand for lipoprotein receptors.

A signaling pathway involving the extracellular protein Reelin and the intracellular adaptor protein Disabled-1 (Dab1) controls cell positioning during mammalian brain development. Here, we demonstrate that Reelin binds directly to lipoprotein receptors, preferably the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). Binding requires calcium, and it is inhibited in the presence of apoE. Furthermore, the CR-50 monoclonal antibody, which inhibits Reelin function, blocks the association of Reelin with VLDLR. After binding to VLDLR on the cell surface, Reelin is internalized into vesicles. In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2.

Animals↗
PubMed1998

Cerebellar abnormalities in the disabled (mdab1-1) mouse.

A mouse homolog of the Drosophila Disabled (dab) gene, disabled-1 (mdab1), encodes an adaptor molecule that functions in neural development. Targeted disruption of the mdab1 gene (mdab1-1 mice) leads to anomalies in the development of the cerebrum, hippocampus, and cerebellum. Here we describe a number of histologic abnormalities in the cerebellum of the mdab1-1 mouse. There is a complete absence of foliation, and most Purkinje cells are clumped in central clusters. However, lamination appears to develop normally in areas where the Purkinje cells and external granular layer are closely apposed. The granular layer forms a thin rind over most of the cerebellar surface, but is subdivided by both transverse and parasagittal boundaries. The Purkinje cells, identified by anti-zebrin II in the adult or anti-calbindin in the new born mdab1-1 mutant cerebellum, form a parasagittal banding pattern, similar to but distorted compared with the wild-type design. The data suggest that the development of the mdab1-1 cerebellum parallels the development of reeler. The reeler gene encodes an extracellular protein (Reelin) that is secreted by the external granular layer. Because Reelin expression is retained in the mdab1-1 mutant mouse, mDab1 p80 may act in a parallel pathway or downstream of Reelin, leading to the transformation of embryonic Purkinje cell clusters into the adult parasagittal bands.

Animals↗
PubMed1999

Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation.

The large extracellular matrix protein Reelin is produced by Cajal-Retzius neurons in specific regions of the developing brain, where it controls neuronal migration and positioning. Genetic evidence suggests that interpretation of the Reelin signal by migrating neurons involves two neuronal cell surface proteins, the very low density lipoprotein receptor (VLDLR) and the apoE receptor 2 (ApoER2) as well as a cytosolic adaptor protein, Disabled-1 (Dab1). We show that Reelin binds directly and specifically to the ectodomains of VLDLR and ApoER2 in vitro and that blockade of VLDLR and ApoER2 correlates with loss of Reelin-induced tyrosine phosphorylation of Disabled-1 in cultured primary embryonic neurons. Furthermore, mice that lack either Reelin or both VLDLR and ApoER2 exhibit hyperphosphorylation of the microtubule-stabilizing protein tau. Taken together, these findings suggest that Reelin acts via VLDLR and ApoER2 to regulate Disabled-1 tyrosine phosphorylation and microtubule function in neurons.

Animals↗
PubMed2000

[Corticohistogenesis and Reelin signal cascade].

Corticohistogenesis follows highly regulated spatial and temporal patterns of cell proliferation, neuronal migration and neuronal differentiation to generate the characteristic cortical layers. We gained several insights into the mechanisms of the processes how a class of neurons attains an appropriate layer in developing neocortex. Using a neurological mutant mice reeler, we identified that the extracellular matrix protein Reelin that is specifically secreted from the Cajal-Retzius cells regulates the positioning of the cortical plate neurons. There has identified that Dab1 is one of the intracellular signaling components that respond to Reelin. Recently, three membrane proteins, apoER2, VLDLR and CNR are identified to bind Reelin. The double mutant--apoER2-/-; vldlr-/(-)--shows a phenotype indistinguishable from Reelin deficient mice. The CNRs are originally isolated through the interaction of their intracellular domain with Fyn, a member of the Src kinase family. The antibodies against Reelin or CNR disrupted Reelin-CNR binding. These three classes of membrane proteins are thought to act in concert as components of the Reelin receptor.

Animals↗
PubMed2000

Entorhinal cortex lesion does not alter reelin messenger RNA expression in the dentate gyrus of young and adult rats.

The extracellular matrix protein reelin plays an important role in neuronal pattern formation and axonal collateralization during the development of the central nervous system. With the concept that reelin might also be important for axonal growth in the injured nervous system we investigated whether reelin is re-expressed in areas of collateral sprouting after brain injury. The expression of reelin messenger RNA was studied in the denervated fascia dentata of adult rats one, four, seven and 14 days following entorhinal cortex lesion. In adult control animals, in situ hybridization histochemistry with digoxigenin-labeled reelin riboprobes revealed reelin messenger RNA expression in neurons located in the outer molecular layer and beneath the granule cell layer of the dentate gyrus. After entorhinal cortex lesion, this expression pattern did not change during the whole post-lesional time period investigated despite a strong glial activation and reactive sprouting in the outer molecular layer of the dentate gyrus as visualized by immunohistochemistry for glial fibrillary acidic protein and acetylcholinesterase histochemistry, respectively. The expression of reelin messenger RNA was also unaffected by entorhinal cortex lesion in the dentate gyrus of young animals (postnatal day seven), where an even stronger sprouting response occurs.

Age Factors↗
PubMed2000

Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression.

Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.

Adult↗
PubMed1997

Disruption of hippocampal development in vivo by CR-50 mAb against reelin.

We previously generated a monoclonal alloantibody, CR-50, by immunizing reeler mutant mice with homogenates of normal embryonic brains. This antibody recently was shown to recognize a Reelin protein, which is coded by the recently identified candidate gene for the reeler mutation. However, it is still unclear whether Reelin, especially the CR-50 epitope region, is indeed responsible for the reeler phenotype in vivo. Here we show that Reelin is localized on Cajal-Retzius neurons in the hippocampus and that intraventricular injection of CR-50 at the embryonic stage disrupts the organized development of the hippocampus in vivo, converting it to a reeler pattern. Labeling experiments with 5-bromodeoxyuridine demonstrated that the labeled cells in the stratum pyramidale of the CR-50-treated mice were distributed in a pattern similar to that of reeler. Thus, Cajal-Retzius neurons play a crucial function in hippocampus development, and the CR-50 epitope on Reelin plays a central role in this function.

Animals↗
PubMed1999

Presenilin-1 deficiency leads to loss of Cajal-Retzius neurons and cortical dysplasia similar to human type 2 lissencephaly.

BACKGROUND: Presenilin-1 (PS1) is a transmembrane protein that is located in the endoplasmic reticulum and the cis Golgi apparatus. Missense mutations of PS1 that modify gamma-secretase function, leading to a pathologic processing of amyloid precursor protein, are an important cause of familial Alzheimer's disease. Physiologically, the presenilins are involved in the Notch and Wnt-beta-catenin signaling pathways. RESULTS: PS1-deficient mice develop a cortical dysplasia resembling human type 2 lissencephaly, with leptomeningeal fibrosis and migration of cortical-plate neurons beyond their normal position into the marginal zone and subarachnoid space. This disorder of neuronal migration is associated with the disappearance of the majority of the cells of the marginal zone, notably most of the Cajal-Retzius pioneer neurons, between embryonic days E14 and E18, and is preceded and accompanied by disorganization of Notch-1 immunoreactivity on the neuronal cell membranes. The marginal zone also becomes depleted of the extracellular matrix protein reelin and chondroitin sulfate proteoglycans. At that stage PS1 is transiently expressed in leptomeningeal fibroblasts, which are mandatory for the trophic support of Cajal-Retzius neurons. CONCLUSIONS: In agreement with models in which neuronal migration disorders have been linked to a defect in Cajal-Retzius cells, the loss of most of these cells in PS1-deficient mice leads to cortical dysplasia. Because PS1 is normally expressed in the leptomeninges, and these become fibrotic in the PS1-knockout mice, we favor the hypothesis that the loss of Cajal-Retzius cells is caused by a defective trophic interaction with leptomeningeal cells, possibly involving disruption of Notch signaling.

Amyloid Precursor Protein Secretases↗
PubMed1999

Hippocampal Cajal-Retzius cells project to the entorhinal cortex: retrograde tracing and intracellular labelling studies.

Cajal-Retzius (CR) cells are characteristic horizontally orientated, early-generated transient neurons in the marginal zones of the neocortex and hippocampus that synthesize the extracellular matrix protein reelin. They have been implicated in the pathfinding of entorhino-hippocampal axons, but their role in this process remained unclear. Here we have studied the axonal projection of hippocampal CR cells. Following injection of the carbocyanine dye DiI into the entorhinal cortex of aldehyde-fixed rat embryos and young postnatal rats, neurons in the outer molecular layer of the dentate gyrus and stratum lacunosum-moleculare of the hippocampus proper with morphological characteristics of CR cells were retrogradely labelled. In a time course analysis, the first retrogradely labelled CR cells were observed on embryonic day 17. This projection of hippocampal CR cells to the entorhinal cortex was confirmed by retrograde tracing with Fast Blue in new-born rats and by intracellular biocytin filling of CR cells in acute slices from young postnatal rat hippocampus/entorhinal cortex and in entorhino-hippocampal slice cocultures using infrared videomicroscopy in combination with the patch-clamp technique. In double-labelling experiments CR cells were identified by their immunocytochemical staining for reelin or calretinin, and their interaction with entorhino-hippocampal axons labelled by anterograde tracers was analysed. Future studies need to investigate whether this early transient projection of hippocampal CR cells to the entorhinal cortex is used as a template by the entorhinal axons growing to their target layers in the hippocampus.

Amidines↗
PubMed1998

Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats.

During embryonic development of brain laminated structures, the protein Reelin, secreted into the extracellular matrix of the cortex and hippocampus by Cajal-Retzius (CR) cells located in the marginal zone, contributes to the regulation of migration and positioning of cortical and hippocampal neurons that do not synthesize Reelin. Soon after birth, the CR cells decrease, and they virtually disappear during the following 3 weeks. Despite their disappearance, we can quantify Reelin mRNA (approximately 200 amol/ g of total RNA) and visualize it by in situ hybridization, and we detect the translated product of this mRNA by immunocytochemistry preferentially in gamma-aminobutyric acid (GABA)ergic neurons of adult rat cortex and hippocampus. In adult rat cerebellum, Reelin is expressed in glutamatergic neurons (granule cells). The translated product of this mRNA is readily exported from the granule cell somata to the parallel fibers, where it has been detected by electron microscopy in axon terminals located presynaptically to Purkinje cell dendrites.

Animals↗