Neuronal chain gangs: homotypic contacts support migration into the olfactory bulb.

The role of glia in the migration of the olfactory interneuron progenitors has yet to be determined. The results of the explant culture studies (Hu et al. 1996xHu, H, Tomasiewicz, H, Magnuson, T, and Rutishauser, U. Neuron. 1996; 16: 735–743Abstract | Full Text | Full Text PDF | PubMed | Scopus (297)See all ReferencesHu et al. 1996) indicate that glia are not necessary for their migration. Certainly, glia do not serve as a direct migratory substrate, a role that radial glia play in other areas of the brain (Rakic 1990xRakic, P. Experientia. 1990; 46: 882–891Crossref | PubMed | Scopus (468)See all ReferencesRakic 1990). In the adult olfactory bulb, however, they may contribute to these movements in several ways (Lois et al. 1996xLois, C, Garcia-Verdugo, J.-M, and Alvarez-Buylla, A. Science. 1996; 271: 978–981Crossref | PubMedSee all ReferencesLois et al. 1996). The glial processes that ensheath the migrating neuroblasts may provide a permissive environment for the migration through the adult brain, they may actively guide the cells to the olfactory bulb, or they may restrict them from dispersing into other regions of the brain. Migrating neuroblasts in the neonatal do not appear to be surrounded by glial processes as has been shown in the adult (Kishi et al. 1990xKishi, K, Peng, J.Y, Kakuta, S, Murakami, K, Kuroda, M, Yokata, S, Hayakama, S, Kuge, T, and Asayama, T. Arch. Histol. Cytol. 1990; 53: 219–226Crossref | PubMedSee all ReferencesKishi et al. 1990). Thus, it is possible that the glia play a more active role in the tangential olfactory interneuron migration as the animals mature.An additional question is whether the mechanism described here is applicable to other types of tangential migration in the developing brain. In the tectum, young tectobulbar neurons appear to travel tangentially along axons extended by older members of the same neuronal class (Gray and Sanes 1991xGray, G.E and Sanes, J.R. Neuron. 1991; 6: 211–225Abstract | Full Text PDF | PubMed | Scopus (97)See all ReferencesGray and Sanes 1991). While homotypic contacts may support these movements, the underlying mechanism would be defined as axonophilic (Rakic 1990xRakic, P. Experientia. 1990; 46: 882–891Crossref | PubMed | Scopus (468)See all ReferencesRakic 1990). Both neurons (O'Rourke et al. 1992xO'Rourke, N.A, Dailey, M.E, Smith, S.J, and McConnell, S.K. Science. 1992; 258: 425–427CrossrefSee all ReferencesO'Rourke et al. 1992) and neural progenitors (Fishell et al., 1993) migrate tangentially in the main body of the developing cerebral cortex, and the mechanisms for their migration remain a mystery. Tangentially oriented neurons in the intermediate zone of the dorsal cortex extend their leading processes orthogonal to the radial glia (O'Rourke et al. 1995xO'Rourke, N.A, Sullivan, D.P, Kaznowski, C.E, Jacobs, A.A, and McConnell, S.K. Development. 1995; 122: 2165–2176See all ReferencesO'Rourke et al. 1995), yet they appear to be dispersed rather than in close contact with one another. These neurons do not travel along the length of glial processes as radially migrating neurons do, but they contact both radial glia and axons along their route and may undergo axonophilic migration. In the ventricular zone, rounded neural progenitors disperse from one another through random movements in the tangential plane of the ventricular zone (Fishell et al., 1993). Both the shapes of these progenitor cells and their mode of movement appear to distinguish them from the olfactory neuroblasts. Thus, neither of these migratory populations appear likely to employ a migratory mechanism similar to that of the aSVZ neuroblasts. A group of neurons that express class III β-tubulin also appear to migrate tangentially through the proliferative zones of the cerebral cortex (10xMenezes, J.R and Luskin, M.B. J. Neurosci. 1994; 14: 5399–5416PubMedSee all References, 14xO'Rourke, N.A, Sullivan, D.P, Kaznowski, C.E, Jacobs, A.A, and McConnell, S.K. Development. 1995; 122: 2165–2176See all References). The possibility that these cells rely on homotypic contacts for their movement has yet to be explored. Thus, while a homophilic mechanism does not appear to account for all instances of tangential migration, other regions of the brain and spinal cord should be examined closely to determine whether it could be invoked more broadly.Previous investigators have characterized populations of neurons that undergo either glial-guided or axon-guided migration (Rakic 1990xRakic, P. Experientia. 1990; 46: 882–891Crossref | PubMed | Scopus (468)See all ReferencesRakic 1990). The studies on the olfactory bulb discussed here define a new category of “self-guided” migration based on homotypic interactions that are mediated, in part, by polysialic acid residues on NCAM. Many questions remain to be answered with regard to this mechanism. One wonders about the nature of the cellular behavior within the neuronal chains. Do the cells slide or “leap frog” past each other in a dynamic fashion, or do they maintain static contacts and move like a large conveyor belt? How do cells within the olfactory bulb leave the chains and migrate radially? Finally, what other molecules help drive the cells toward the olfactory bulb? Do diffusible signals attract the cells, or is the environment simply more permissive for movements in the rostral direction? Clearly, the studies in the olfactory bulb will spark further interest into the cellular and molecular cues that guide migrating cells in all regions of the brain.