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      Cell migration in the postnatal subventricular zone

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          Abstract

          New neurons are constantly added to the olfactory bulb of rodents from birth to adulthood. This accretion is not only dependent on sustained neurogenesis, but also on the migration of neuroblasts and immature neurons from the cortical and striatal subventricular zone (SVZ) to the olfactory bulb. Migration along this long tangential pathway, known as the rostral migratory stream (RMS), is in many ways opposite to the classical radial migration of immature neurons: it is faster, spans a longer distance, does not require radial glial guidance, and is not limited to postmitotic neurons. In recent years many molecules have been found to be expressed specifically in this pathway and to directly affect this migration. Soluble factors with inhibitory, attractive and inductive roles in migration have been described, as well as molecules mediating cell-to-cell and cell-substrate interactions. However, it is still unclear how the various molecules and cells interact to account for the special migratory behavior in the RMS. Here we will propose some candidate mechanisms for roles in initiating and stopping SVZ/RMS migration.

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          Most cited references68

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          Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone.

          M B Luskin (1993)
          The subventricular zone of the postnatal forebrain produces mainly glia, although it supports limited neurogenesis. To determine whether the subventricular zone is positionally specified, the phenotype and destination of the progeny of subventricular zone cells along the anterior-posterior axis of the lateral ventricles were analyzed. A retroviral lineage tracer containing the E. coli reporter gene lacZ was injected into different parts of the subventricular zone of neonatal rat pups, and at various times thereafter, the expression of beta-galactosidase was detected histochemically or immunohistochemically in the descendants of infected cells. A discrete region of the anterior part of the subventricular zone (SVZa) generated an immense number of neurons that differentiated into granule cells and periglomerular cells of the olfactory bulb-the two major types of interneurons. Thus, the SVZa appears to constitute a specialized source of neuronal progenitor cells. To reach the olfactory bulb, neurons arising in the SVZa migrate several millimeters along a highly restricted route. Guidance cues must be involved to prohibit widespread dispersion of these migrating neurons.
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            Central nervous system neuronal migration.

            Widespread cell migrations are the hallmark of vertebrate brain development. In the early embryo, morphogenetic movements of precursor cells establish the rhombomeres of the hindbrain, the external germinal layer of the cerebellum, and the regional boundaries of the forebrain. In midgestation, after primary neurogenesis in compact ventricular zones has commenced, individual postmitotic cells undergo directed migrations along the glial fiber system. Radial migrations establish the neuronal layers. Three molecules have been shown to function in glial guided migration--astrotactin, glial growth factor, and erbB. In the postnatal period, a wave of secondary neurogenesis produces huge numbers of interneurons destined for the cerebellar cortex, the hippocampal formation, and the olfactory bulb. Molecular analysis of the genes that mark stages of secondary neurogenesis show similar expression patterns of a number of genes. Thus these three regions may have genetic pathways in common. Finally, we consider emerging studies on neurological mutant mice, such as reeler, and human brain malformations. Positional cloning and identification of mutated genes has led to new insights on laminar patterning in brain.
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              Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes.

              Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Braz J Med Biol Res
                Associação Brasileira de Divulgação Científica (Ribeirão Preto )
                1414-431X
                December 2002
                : 35
                : 12
                : 1411-1421
                Affiliations
                [1 ] Universidade Federal do Rio de Janeiro Brazil
                [2 ] Universidade Federal do Rio de Janeiro Brazil
                Article
                S0100-879X2002001200002
                10.1590/S0100-879X2002001200002
                4035b85f-2b56-4200-8440-3c7f3f94c00b

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-879X&lng=en
                Categories
                BIOLOGY
                MEDICINE, RESEARCH & EXPERIMENTAL

                Medicine,General life sciences
                Postnatal neurogenesis,Chain migration,Rostral migratory stream,Astrocytes,Gap junctions,Radial glia

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