Migration Of Neuronal Precursors Research Articles

Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice.

In the brain of adult mice, cell division persists in the subventricular zone (SVZ) of the lateral ventricles. These SVZ cells migrate rostrally 3-5 mm to the olfactory bulb, where they differentiate into neurons. We have investigated the distribution of PSA-N-CAM in the adult mouse forebrain. Immunoreactivity for PSA-N-CAM precisely reveals the migratory pathway of SVZ cells. This pathway of PSA-N-CAM positive cells starts in the lateral wall of the lateral ventricle, where immunopositive cells form weblike patterns. The PSA-N-CAM positive pathway extends rostrally between the corpus callosum and the striatum into the anterior ventral telencephalon, and then into the core of the olfactory bulb. Experiments in which [3H]-thymidine was injected systemically indicated that the majority of the dividing cells on the SVZ of the lateral ventricle and along the migratory pathway are positive to PSA-N-CAM or closely associated with PSA-N-CAM. Microinjection of [3H]-thymidine into the SVZ of the lateral ventricle to label a small patch of dividing SVZ cells shows that neuroblasts that migrated away from the injection site are positive or are closely associated with other cells that are positive for PSA-N-CAM. Migrating cells are tethered together, forming long chains of immunopositive cells. The migratory pathway is formed by 30-40 of these immunopositive chains. Radially oriented individual PSA-N-CAM positive cells were observed in the olfactory bulb. These cells seem to have broken away from chains of immunopositive cells in the core of the olfactory bulb and to be migrating to more superficial layers. Little is known about the mechanisms of tangential migration during development and in adulthood. The cell-cell arrangement revealed by PSA-N-CAM staining suggests new models for this form of neuronal migration. PSA-N-CAM localization along the migratory pathway to the olfactory bulb suggests that in the adult brain this molecule plays a role in migration of neuronal precursors.

Contribution of RGD sequence to neuronal migration in developing cerebral cortex.

The RGD sequence (Arg-Gly-Asp) is known to bind integrins and the synthetic RGD tripeptide inhibits cell adhesion and migration of cultured neuronal cells. However, it is not known whether migration of neuronal precursors in vivo during the cortical histogenesis of the mammalian telencephalon depends on the RGD sequence. To examine this possibility, the RGD peptide was injected into the telencephalic vesicle of mouse embryos. A hypoplastic cortical plate was induced and histological analysis and BrdU-immunohistochemistry revealed that the RGD sequence is involved in neuronal migration and proliferation in the telencephalon during formation of the cortical plate.

NT-3, BDNF, and NGF in the developing rat nervous system: Parallel as well as reciprocal patterns of expression

To obtain insight into the site and stage specificity of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) action in vivo, we compared the expression patterns of the genes for these three related neurotrophic factors as well as for the NGF receptor in developing and adult rats. Initial embryonic expression of these related neurotrophic factors approximately coincides with the onset of neurogenesis. However, the levels at which the three factors are expressed at this time and throughout the developing nervous system are dramatically different. NT-3 is by far the most highly expressed in immature regions of the CNS in which proliferation, migration, and differentiation of neuronal precursors is ongoing. NT-3 expression dramatically decreases with maturation of these regions. By contrast, BDNF expression is low in developing regions of the CNS and increases as these regions mature. NGF expression varies during the development of discrete CNS regions, but not in any consistent manner compared with NT-3 and BDNF Despite the dramatic variations, NT-3, BDNF, and NGF do share one striking similarity-high level expression in the adult hippocampus. Our observations are consistent with the idea that NT-3, BDNF, and NGF have parallel as well as reciprocal roles in vivo.