Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb

doi:10.1016/0306-4522(94)90333-6

Neuroscience

Volume 62, Issue 1, September 1994, Pages 291-305

https://doi.org/10.1016/0306-4522(94)90333-6 Get rights and content

Abstract

The highly sialylated isoform of the neural cell adhesion molecule is thought to be expressed predominantly in the developing nervous system, where it is implicated in a variety of dynamic events linked to neural morphogenesis. It has become increasingly evident, however, that this “embryonic” neural cell adhesion molecule isoform continues to be expressed in certain adult neuronal systems, and in particular, in those that can undergo structural plasticity. In the present study, we performed light microscopic immunocytochemistry with an antibody specific for polysialylated neural cell adhesion molecule and confirmed our earlier observations [Bonfanti L. et al. (1992) Neuroscience 49, 419–436] showing polysialylated neural cell adhesion molecule-immunoreactive cells in the subependymal layer of the lateral ventricle of the adult rat, a region where cell proliferation continues into the postnatal period. In addition, we used an antibody raised against the proliferating cell nuclear antigen and found that proliferating cells continue to be visible in this area, even in the adult. Double immunolabeling showed that many of these newly generated cells displayed high polysialylated neural cell adhesion molecule immunoreactivity. Cells from a portion of the subependymal layer migrate to the olfactory bulb and contribute to the continual replacement of its granule neurons [Luskin M.B. (1993) Neuron 11, 173–189]. We found polysialylated neural cell adhesion molecule-immunoreactive cells all along the pathway purported to be followed by the newly generated cells to their final destination and in neurons corresponding to granular and periglomerular cells in the olfactory bulb.

Our present observations thus support the contention that polysialylation is a feature of neurons capable of dynamic change and may contribute to the molecular mechanisms permitting cell proliferation and migration not only during development but also in the adult.

References (44)

AaronL.I. et al.
Heterogeneous distribution of polysialylated neuronal-cell adhesion molecule during post-natal development and in the adult: an immunohistochemical study in the rat brain
Neuroscience
(1989)
BonfantiL. et al.
Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study
Neuroscience
(1992)
LevisonS.W. et al.
Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain
Neuron
(1993)
LuskinM.B.
Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone
Neuron
(1993)
MiragallF. et al.
Expression of cell adhesion molecules in the olfactory system of the adult mouse: presence of the embryonic form of N-CAM
Devl Biol.
(1988)
RakicP.
Guidance of neurons migrating to the fetal monkey neocortex
Brain Res.
(1971)
RutishauserU. et al.
Polysialic acid on the surface of axons regulates patterns of normal and activity-dependent innervation
Trends Neurosci.
(1991)
ShuS. et al.
The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system
Neurosci. Lett.
(1988)
TheodosisD.T. et al.
Activity-dependent neuronal-glial and synaptic plasticity in the adult mammalian hypothalamus
Neuroscience
(1993)
AchesonA. et al.
NCAM polysialie acid can regulate both cell-cell and cell-substrate interactions
J. Cell Biol.
(1991)

AltaianJ.

Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb

J. comp. Neurol.

(1969)

BayerS.A.

³H-Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb

Expl Brain Res.

(1983)

BoisseauS. et al.

Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development

Development

(1991)

Boulder Committee

Embryonic vertebrate central nervous system: revised terminology

Anat. Rec.

(1970)

CremerH. et al.

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning

Nature

(1994)

EdelmanG.M.

Modulation of cell adhesion during induction, histogenesis, and perinatal development of the nervous system

A. Rev. Neurosci.

(1984)

EdelmanG.M. et al.

Cell adhesion molecules in neural morphogenesis

EdelmanG.M. et al.

Cell adhesion molecules: implications for a molecular histology

A. Rev. Biochem.

(1991)

GlobusJ.H. et al.

The subependymal cell plate (matrix) and its relationship to brain tumors of the ependymal type

J. Neuropath.

(1944)

GraziadeiP.P.C. et al.

Continuous nerve cell renewal in the olfactory system

HallP.A. et al.

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms

J. Path.

(1990)

HindsJ.W.

Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration

J. comp. Neurol.

(1968)

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Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb

Abstract

Neuroscience

Neuroscience

Neuron

Neuron

Devl Biol.

Brain Res.

Trends Neurosci.

Neurosci. Lett.

Neuroscience

NCAM polysialie acid can regulate both cell-cell and cell-substrate interactions

J. Cell Biol.

Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb

J. comp. Neurol.

3H-Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb

Expl Brain Res.

Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development

Development

Embryonic vertebrate central nervous system: revised terminology

Anat. Rec.

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning

Nature

Modulation of cell adhesion during induction, histogenesis, and perinatal development of the nervous system

A. Rev. Neurosci.

Cell adhesion molecules in neural morphogenesis

Cell adhesion molecules: implications for a molecular histology

A. Rev. Biochem.

The subependymal cell plate (matrix) and its relationship to brain tumors of the ependymal type

J. Neuropath.

Continuous nerve cell renewal in the olfactory system

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms

J. Path.

Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration

J. comp. Neurol.

³H-Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb