The reeler gene-associated antigen on cajal-retzius neurons is a crucial molecule for laminar organization of cortical neurons

“…that they produce reelin, a glycoprotein essential for orderly neuronal cell migration and ingrowth of afferents into the cerebral cortex, has augmented this attention (D’Arcangelo et al., 1995, 1997; Ogawa et al., 1995; Del Rio et al., 1997; Nakajima et al., 1997; Curran and D’Arcangelo, 1998).”

“Recently, studies reporting that reelin, the gene product affected in the reeler mutation, is expressed by Cajal-Retzius cells have strongly indicated a role for these neurons in migration (D’Arcangelo et al., 1995; Hirotsune et al., 1995; Ogawa et al., 1995).”

“…of Reelin immunoreactivity in the cerebral cortex of hypothyroid rats To investigate whether Reelin distribution was also altered in hypothyroid rats, brain sections were immunostained with the CR50 mAb that recognizes the N-terminal region of Reelin (Ogawa et al., 1995; D’Arcangelo et al., 1997).”

“Recent findings suggest that they are important developmentally (Ogawa et al., 1995); however, their fate in the adult cortex has not been resolved.”

“…marginal zones were Cajal–Retzius cells, we carried out a double-labeling experiments using confocal microscopy for the mGluRs and for reelin, an extracellular matrix glycoprotein that is synthesized and secreted by Cajal–Retzius cells (D'Arcangelo et al., 1995, 1997; Ogawa et al., 1995).”

“and Dendritic Golgi Deployment”

“However, subsequent cohorts of neurons are unable to bypass to Neuronal Positioning Previous study on reeler mice showed that the earliest their predecessors (Caviness, 1982; Ogawa et al., 1995; Sheppard and Pearlman, 1997) and, thus, accumulate cortical neurons of the preplate are misoriented (J.”

“RELN is a large extracellular matrix (ECM)-like secreted protein (D’Arcangelo et al. 1995; Hirotsune et al. 1995) produced by the Cajal-Retzius cells lining the outer layer of the preplate (Ogawa et al. 1995).”

“These cells are important for correct positioning of cortical neurons because they are the main source of the extracellular matrix protein reelin, which is critically involved in the inside-out corticogenetic migration gradient (D’Arcangelo et al., 1995; Ogawa et al., 1995).”

“…aredeficient inReelin expression (Caviness, ginal zone do contain aggregations of Reelin-expressing CR cells, which as such could represent localized sitesJr. et al., 1988; Ogawa et al., 1995). of greater Reelin production, as compared with regions of the marginal zone devoid of invaginations.”

“When the culture medium is subjected to immunoprecipitation with the anti-reelin monoclonal antibody CR-50 (Ogawa et al., 1995; D’Arcangelo et al., 1997), a major protein of ;400 kDa is present in samples from normal cerebellum (Fig.”

“Studies in the reeler mutant mouse showing that the reelin gene is expressed in CR cells indicated a role for these early neurons in migration and cortical lamination (D’Arcangelo et al., 1995; Hirotsune et al., 1995; Ogawa et al., 1995).”

“Reelin, the product of the reeler gene (40), is synthesized and secreted in the cerebral cortex, predominantly by the Cajal-Retzius cell of the marginal zone, the outermost layer of the developing cortex (40,41).”

“In early corticogenesis, Reelin stimulates neuronal migration by attracting leading processes and inducing their branching and attachment to the ECM (Ogawa et al., 1995; Tissir and Goffinet, 2003; Franco et al., 2011).”

“…in primary antibody diluted in 2% BSA-PBS for 2 h. Primary antibodies and their dilutions used in this study were as follows: Reelin (CR50; 1:1000; Ogawa et al., 1995), Tbr1 (AB9616; 1:500; Millipore, Billerica, MA), Brn1 (SC-6028; 1:100; Santa Cruz Biotechnology, Santa Cruz, CA), MAP2 (M1406;…”

“MINI REVIEW published: 09 May 2016 doi: 10.3389/fncel.2016.00122 New Insights into Reelin-Mediated Signaling Pathways Gum Hwa Lee 1* and Gabriella D’Arcangelo 2 1 College of Pharmacy, Chosun University, Gwangju, South Korea, 2 Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Pi…”

“…the ability of migrating neurons to split the PP and the ability of radial glia–guided neurons to migrate past older neurons to generate the inside-out pattern of cortical layering (D’Arcangelo et al. 1995, Leemhuis & Bock 2011, Marín et al. 2010, Ogawa et al. 1995, Stranahan et al. 2013).”

“Because several studies have shown that altered reelin expression in corticogenesis disrupts the normal laminar and columnar organization of the cerebral cortex ( Ogawa et al., 1995; Nishikawa et al., 2002), our findings suggest that embryonic serotonergic disturbances may have an impact on the late stages of corticog…”

“The EGF-like motifs in reelin have the highest similarity with the extracellular matrix proteins tenascin, restrictin, and the integrin [3-chain family (Reichardt and Tomaselli 1991).”

“When applied to mouse brain sections, R4B and R5A detected immunopositive cells similar to those stained with validated anti-Reelin antibodies (Ogawa et al., 1995; de Bergeyck et al., 1998), or revealed by in situ hybridization with Reelin probes (Schiffmann et al., 1997; Alcantara et al., 1998).”

“, 1997) was obtained as described previously (Ogawa et al., 1995).”

“Binding of Reln to the receptors is inhibited by mAb CR-50, which blocks Reln function in vivo and in vitro (D’Arcangelo et al. 1995, 1999; Ogawa et al. 1995; Del Rio et al. 1997; Nakajima et al. 1997).”

“Reelin is a marker specific for Cajal-Retzius neurons and is required for proper cortical lamination (D’Arcangelo et al., 1995; Ogawa et al., 1995).”

“Finally, comparison of the cerebellar phenotype of the chimera with the previously described reeler and scrambler/yotari mutants (Ogawa et al., 1995; Sweet et al., 1996; Gilmore and Herrup, 1997; Goldowitz et al., 1997; Gonzalez et al., 1997; Howell et al., 1997b; Sheldon et al., 1997; Ware et al.,…”

“The molecular basis of the reeler trait is being unraveled (Bar et al., 1995; D’Arcangelo et al., 1995; Hoffarth et al., 1995; Ogawa et al., 1995), and its effects on cortical cell migration, architectonics, and connectivity are well known (Caviness et al., 1988).”

“The extracellular matrix protein reelin has been proposed recently as a typical product of these cells (D’Arcangelo et al., 1995; Hirotsune et al., 1995; Ogawa et al., 1995).”

“The architectural development of the cortical plate is known to depend on the presence of transient pioneer neurons — the Cajal–Retzius cells — within the marginal zone, and a specific organization of the local extracellular matrix [25–28].”

“…in naturally occurring cell death during development include (1) excitotoxic effects caused by afferents resulting in neuronal hyperexcitability (Choi, 1988; Oppenheim, 1991) and (2) competition for target-derived factors such as growth factors (Davies, 1988, 1994; Silos-Santiago et al., 1995).”

“It was accordingly concluded that a reeler-geneassociated antigen of CR cells is important for the normal development of these regions and that its absence in reeler mice plays a role in the malformations observed in this mutant ( Ogawa et al. 1995 ).”

“Moreover, recent advances in the molecular genetics underlying certain neurological mutations (D’Arcangelo et al., 1995; Hirotsune et al., 1995; Ogawa et al., 1995; Rakic and Caviness, 1995) will render these animals even more valuable for clarifying basic features of normal and abnormal…”

“In contrast, al., 1995; Ogawa et al., 1995; Hu et al., 1996; Zheng et the role of CR cells in migration is supported by: (i) the al., 1996), and the proteins recognized by the D4 and constant correlation between the survival and location NJPA1 antibodies (Anton et al., 1996), have a critical of CR…”

“…from the Cajal-Retzius cells in the MZ and activates Disabled homolog 1 (Dab1) in migrating neurons, plays indispensable roles in this inside-out neuronal positioning (Caviness and Sidman, 1973; D’Arcangelo et al., 1995; Ogawa et al., 1995; Rice and Curran, 2001; Tissir and Goffinet, 2003).”

“Loss of Cajal-Retzius cells (or reelin expression) results in loss of the inside-out pattern of radial migration required to generate the normal laminar organization of the neocortex (Ogawa et al., 1995; Super et al., 2000).”

“Antibody CR-50 prevents dimerization and blocks Reelin function in vitro and in vivo (Ogawa et al., 1995; Del Rio et al., 1997; Nakajima et al., 1997; Kubo et al., 2002; Zhao et al., 2004).”

“Incubation of hippocampal co-cultures with the CR-50 antibody against reelin During the first 3 days after preparation, 1 µl of CR-50 [100 µg/ml, diluted in sterile saline; kindly provided by Dr M. Ogawa (see Ogawa et al., 1995)] was added to each hippocampal co-culture 3 times a day (n=9).”

“The ages of the embryos and fetuses were estimated on the basis of weeks after ovulation, crown-rump length (Olivier and Pineau, 1962), and anatomical landmarks (O'Rahilly et al., 1987).”

“The signal to terminate neuronal New Haven, Connecticut 06510 cell migration is thought to be provided either by the afferent fibers that migrating neurons encounter near their target location or by the ambient neuronal cell population that had already reached their final position Summary (D’Arcangelo et al., 1995; Ha…”

“The overrepresentation of atypical bands (partial, intermediate and pachygyria-SBH), the paucity of classical diffuse and anteriorly predominating SBH, and the predominance of sporadic cases in males suggests that mutations of other genes responsible for corticogenesis (D'Arcangelo et al., 1995; Ogawa et al., 1995; Ra…”

“Reelin is a glycoprotein with serine protease activity (Quattrocchi et al., 2002) and a relative molecular mass of »388 kDa, which was discovered simultaneously by Ogawa et al. (1995) and D’Arcangelo et al. (1995).”

“This antibody was developed concurrently with the cloning of Reelin, based on the presence of an antigen expressed by Cajal-Retzius cells which was absent in the embryonic forebrain of reeler mice [32].”

“For example, reelin has been proposed to act as a chemoattractant (Gilmore and Herrup, 2000), repellent (Ogawa et al., 1995; Schiffmann et al., 1997), stop (Sheppard and Pearlman, 1997), or detachment (Sheppard and Pearlman, 1997; Dulabon et al., 2000; Sanada et al., 2004) signal for radially…”

“One would like to know whether molecules that are thought to be critically involved with lamination of the cortex or tectum, such as reelin (Ogawa et al., 1995) and integrins (Galileo et al.”

“In reeler mutants, lack of reelin in the marginal zone (Ogawa et al., 1995; D’Arcangelo et al., 1997) results in inverted cortical lamination (Pinto-Lord et al., 1982).”

“Birth-date labeling analysis revealed that the cortical layers are roughly inverted in these mice (Caviness and Sidman, 1973; Mikoshiba et al., 1980; D’Arcangelo et al., 1995; Ogawa et al., 1995; Boyle et al., 2011), suggesting that Reelin regulates the proper inside-out formation of the mammalian neocortex.”

“When a reeler slice was placed next to a wildtype slice in the presence of the monoclonal antibody CR-50, which blocks Reelin function (Ogawa et al., 1995; Nakajima et al., 1997), neither a radial glial scaffold nor a compact granule cell layer developed.”

“antibodies to map the distribution of CR cells, the major source of Reelin at embryonic stages (D’Arcangelo et al., 1995; Ogawa et al., 1995; Alcantara et al., 1998).”

“Reelin, expressed by Cajal-Retzius cells (Ogawa et al., 1995; Frotscher, 1998), is fundamental for the definition of cortical layers (Hamburgh, 1963; Zhao et al., 2004), and acts as a stop signal for migrating neurons (Del Río et al., 1997; Chai et al., 2009).”

“…previous MTLE animal studies demonstrated that seizures may induce abnormal migration of new neurons in the hippocampus (Parent et al., 1997; Jessberger et al., 2005) and rostal migratory stream (Parent et al., 2002) and accelerate their neuronal differentiation (Overstreet-Wadiche et al., 2006).”

“Calretinin, a calcium binding protein, also serves as a marker for Cajal-Retzius cells in the immature cortex of the mouse (Soriano et al., 1994; Ogawa et al., 1995).”

“5E-H) (del Río et al., 1995; Ogawa et al., 1995).”

“…-Robo1, -Robo2 antibodies were provided by F. Murakami and A. Tamada) (Sabatier et al., 2004), Reelin (CR50) (mouse, 1:200; provided by M. Ogawa) (Ogawa et al., 1995) S100 (rabbit, 1:5000; Dako), Tbx21 (rabbit, 1:10000; guinea pig, 1:25000), Thy-1 (rat, 1:200; Santa Cruz Biotechnology),…”

“…may include helping to establish the appropriate cortical cytoarchitecture (Marín-Padilla, 1984a,b; Luskin and Shatz, 1985; Del Río et al., 1995a; Ogawa et al., 1995) and serving as transient recipients for incoming afferents, as has been demonstrated for the subplate neurons of the neocortex…”

“This can be expected because the postnatal primate cerebral wall lacks important structural elements, such as radial glia and CajalRetzius cells, which are responsible for the orderly migration of cortical neurons to their proper positions within the cortex (Rakic, 1990; Ogawa et al., 1995).”