Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system

Tomasiewicz, Henry; Ono, Katsuhiko; Yee, Della; Thompson, Christian; Goridis, Christo; Rutishauser, Urs; Magnuson, Terry

doi:10.1016/0896-6273(93)90228-j

Cited by 451 publications

(258 citation statements)

References 57 publications

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“…In the adult brain, SHIP2 expression was mainly detected in structures containing neural stem cells such as the SVZa, the rostral migratory stream and the olfactory tubercle. The SHIP2 expression was dramatically increased in N-CAM-de¢cient mice which present an accumulation of these progenitor cells in the SVZa and the rostral migratory stream (Tomasiewicz et al, 1993;Chazal et al, 2000). By western blot analysis, we have shown that SHIP2 protein is highly expressed in proliferating neurospheres, a model of undi¡erentiated neural stem cells, and barely detectable in di¡erentiated neurospheres which contain subsets of mature neurons, astrocytes and oligodendrocytes (Reynolds et al, 1992;Ben-Hur et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…1 and 2). Mice de¢cient for all splice variants (Cremer et al, 1994;Chazal et al, 2000) or only the 180-kDa isoform (Tomasiewicz et al, 1993) of N-CAM show an accumulation of migrating precursors from SVZ along the rostral migratory stream leading to a reduction in olfactory bulb size and granule cell density. In order to con¢rm the speci¢city of the SHIP2 expression observed in cells in the SVZa and in the rostral migratory stream and to address the putative e¡ect of N-CAM de¢ciency on SHIP2 level of expression, we examined the expression of SHIP2 mRNA in the adult brain of N-CAM knockout mice.…”

Section: Ship2 Mrna Expression In Adult Brainmentioning

confidence: 99%

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The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice

et al. 2001

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AbstractöThe germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their e¡ects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identi¢ed Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2, SHIP2, has the potential to regulate neuronal development. Using in situ hybridization technique with multiple synthetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic stages and subventricular zones at latter stages of brain and spinal cord and in the sympathetic chain. No signi¢cant expression was seen in di¡erentiated ¢elds. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphery, large expression was detected in muscle and kidney and moderate expression in thyroid, pituitary gland, digestive system and bone. In the adult brain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior subventricular zone, the rostral migratory stream and the olfactory tubercle. SHIP2 was also detected in the choroid plexuses and the granular layer of the cerebellum. The speci¢city of SHIP2 expression in neural stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA signal in neural cell adhesion molecule (N-CAM)-de¢cient mice, which present an accumulation of progenitor cells in the anterior subventricular zone and the rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by western blotting in proliferating neurospheres in culture and its downregulation in non-proliferating di¡erentiated neurospheres.In conclusion, the close correlation between the pattern of SHIP2 expression in the brain and the proliferative and early di¡erentiative events suggests that the phosphatase SHIP2 may have important roles in neural development. ß

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Section: Discussionmentioning

confidence: 99%

Section: Ship2 Mrna Expression In Adult Brainmentioning

confidence: 99%

The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice

et al. 2001

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“…In the present study, the number of proliferating neuronal progenitors that migrated rostrally from the dorsolateral corner of the subependyma to the olfactory bulbs was diminished in the TGF␣ (Ϫ/Ϫ) animals. This proliferation deficit seems to be a mechanistically and spatially distinct effect from the selective migratory deficit of neuronal progenitors to the olfactory bulbs in NCAM (Ϫ/Ϫ) animals (Tomasiewicz et al, 1993;Cremer et al, 1994). Subependymal progenitor cells in the NCAM (Ϫ/Ϫ) mice accumulate in situ, causing an expansion of the subependymal zone, which suggests that proliferation of these progenitor cells is unaffected.…”

Section: Discussion Tgf␣ Regulates the Proliferation Of A Specific Sumentioning

confidence: 99%

“…Recent evidence suggests that the chained migration of neuronal progenitors on top of one another may be the mechanism by which the progeny of the constitutively proliferating progenitors migrate tangentially to the olfactory bulbs, and that PSA-NCAM is the critical factor that regulates the intercellular adhesion in this process (Tomasiewicz et al, 1993;Cremer et al, 1994;Rousselot et al, 1995;Hu et al, 1996;Lois et al, 1996). In the present study, the number of proliferating neuronal progenitors that migrated rostrally from the dorsolateral corner of the subependyma to the olfactory bulbs was diminished in the TGF␣ (Ϫ/Ϫ) animals.…”

Section: Discussion Tgf␣ Regulates the Proliferation Of A Specific Sumentioning

confidence: 99%

Transforming Growth Factor-α Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma

et al. 1997

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The adult mammalian forebrain subependyma contains neural stem cells and their progeny, the constitutively proliferating progenitor cells. Using bromodeoxyuridine labeling to detect mitotically active cells, we demonstrate that the endogenous expression of transforming growth factor-␣ (TGF␣) is necessary for the full proliferation of progenitor cells localized to the dorsolateral corner of the subependyma and the full production of the neuronal progenitors that migrate to the olfactory bulbs. Proliferation of these progenitor cells also is diminished with age (in 23-to 25-months-old compared with 2-to 4-months-old mice), likely because of a lengthening of the cell cycle. Senescence or the absence of endogenous TGF␣ does not affect the numbers of neural stem cells isolated in vitro in the presence of epidermal growth factor. These results suggest that endogenous TGF␣ and the effects of senescence may regulate the proliferation of progenitor cells in the adult subependyma, but that the number of neural stem cells is maintained throughout life.

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“…It is noteworthy that even though several tissues normally express NCAM, most appear unaffected in mice that are homozygous null for NCAM (24,25). One possible explanation for this observation is that some functions of NCAM may over- …”

Section: Rncam a Novel Neuronal Cell Adhesion Molecule 26084mentioning

confidence: 90%

Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

Alenius

Bohm

1997

Journal of Biological Chemistry

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We describe here the cloning of mouse complementary DNAs encoding a novel protein, Rb-8 neural cell adhesion molecule (RNCAM), with a predicted extracellular region of five immunoglobulin C2-type domains followed by two fibronectin type III domains. Alternative splicing is likely to generate two RNCAM isoforms, which are differently attached to the cell membrane. These structural features and overall sequence identity identify this protein as a novel member of a cell adhesion molecule subgroup together with vertebrate neural cell adhesion molecule, Aplysia cell adhesion molecule, and Drosophila fasciclin II. In insects, fasciclin II is present on a restricted subset of embryonic central nervous system axons where it controls selective axon fasciculation. Intriguingly, RNCAM likewise is expressed in subsets of olfactory and vomeronasal neurons with topographically defined axonal projections. The spatial expression RNCAM corresponds precisely to that of certain odorant receptor expression zones of the olfactory epithelium. These expression patterns thus render RNCAM the first described cell adhesion molecule with a potential regulatory role in formation of selective axonal projections important for olfactory sensory information coding.

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Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system

Cited by 451 publications

References 57 publications

The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice

The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice

Transforming Growth Factor-α Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma

Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

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