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On-line version ISSN 1678-2690
An. Acad. Bras. Ciênc. vol.72 n.3 Rio de Janeiro Sept. 2000
GAP JUNCTIONS ARE INVOLVED ON THE MIGRATION OF POSTNATAL SUBVENTRICULAR ZONE CELLS*
JOÃO R.L. MENEZES1,2, MARIA M. FRÓES1,3, MONICA M. MARINS1,2 AND VIVALDO MOURA NETO3
1Laboratório de Neuroanatomia Celular
2Laboratório de Neuroplasticidade
3Lab. Morfogênese Celular, Depto. de Anatomia, ICB,
Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
Progenitor cells within the postnatal subventricular zone are remarkable as they migrate and proliferate simultaneously. These cells and their progeny migrate rostrally to the olfactory bulb where they will differentiate into interneurons. This process, called the rostral migratory stream (RMS), is massive in the first two postnatal weeks, and lingers, somewhat smaller, well into adulthood. Recently, we have demonstrated gap junction mediated cell coupling (GJC) within this layer (Menezes J et al. 2000 Dev Neurosci 22:34). Futhermore, GJC matches spatially the distribution of S-phase cells, and is absent where most migratory cells are concentrated. In another germinal layer, the embryonic ventricular zone, cell coupling has been implicated in maintaining cells in the proliferative cycle (Bittman J et al. 1997 J Neurosci 17:7037). To investigate whether GJC plays a role on the proliferative and migratory behavior of SVZ/RMS, we have used an in vitro approach. Briefly, SVZ explants were obtained from 3-4 days postnatal rat pups and cultured directly over poly-ornithine/polylisine treated coverslips; 12 hours after plating, carbenoxolone (10mM), a pharmacological inhibitor of GJC, was added to the culture medium; 3-5 days later, centrifugal migration was scored in treated and untreated explants. Outward migration was robust in untreated explants, displaying chains of small migrating cells. In treated explants, migration was greatly reduced or absent. This effect was partially reversed after interrupting carbenoxolone treatment and keeping the explants in vitro for two more days. Interestingly, recovered explants, in addition to the small migratory cells, also exhibited elongated cells radiating from the explant, which resembled radial glial cells. Migratory cells were preferentially distributed over these elongated glial cells, and did not seem to form chains as seen in control explants. Our results indicate that gap junction mediated cell coupling may be involved in regulating cell migration of SVZ precursors cells. This effect may be directly over the migratory cells, possibly triggering cell migration. Alternatively, it may be mediated by homo- or heterologous cell coupling of glial supporting cells present within the SVZ. ( June 27, 2000 ).