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          Institute: MPI für biophysikalische Chemie     Collection: Abteilung Eichele     Display Documents

ID: 426864.0, MPI für biophysikalische Chemie / Abteilung Eichele
The repulsive guidance molecule RGMa is involved in the formation of afferent connections in the dentate gyrus.
Authors:Brinks, H.; Conrad, S.; Vogt, J.; Oldekamp, J.; Sierra, A.; Deitinghoff, L.; Bechmann, I.; Alvarez-Bolado, G.; Heimrich, B.; Monnier, P. P.; Mueller, B. K.; Skutella, T.
Date of Publication (YYYY-MM-DD):2004-04-14
Title of Journal:The Journal of Neuroscience
Issue / Number:15
Start Page:3862
End Page:3869
Review Status:not specified
Audience:Not Specified
Abstract / Description:In the developing dentate gyrus, afferent fiber projections terminate in distinct laminas. This relies on an accurately regulated spatiotemporal network of guidance molecules. Here, we have analyzed the functional role of the glycosylphosphatidylinositol (GPI)-anchored repulsive guidance molecule RGMa. In situ hybridization in embryonic and postnatal brain showed expression of RGMa in the cornu ammonis and hilus of the hippocampus. In the dentate gyrus, RGM immunostaining was confined to the inner molecular layer, whereas the outer molecular layers targeted by entorhinal fibers remained free. To test the repulsive capacity of RGMa, different setups were used: the stripe and explant outgrowth assays with recombinant RGMa, and entorhino-hippocampal cocultures incubated either with a neutralizing RGMa antibody (Ab) or with the GPI anchor-digesting drug phosphatidylinositol-specific phospholipase C. Entorhinal axons were clearly repelled by RGMa in the stripe and outgrowth assays. After disrupting the RGMa function, the specific laminar termination pattern in entorhino-hippocampal cocultures was lost, and entorhinal axons entered inappropriate hippocampal areas. Our data indicate an important role of RGMa for the layer-specific termination of the perforant pathway as a repulsive signal that compels entorhinal fibers to stay in their correct target zone.
Free Keywords:axon; dentate; development; guidance; hippocampus; neuron
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Gregor Eichele
MPI für biophysikalische Chemie/AG Alvarez-Bolado
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