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Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis

Abstract

During development, Reelin acts on migrating neuronal precursors and controls correct cell positioning in the cortex and other brain structures by a hitherto unidentified mechanism. Here we show that in the postnatal mouse brain, Reelin acts as a detachment signal for chain-migrating interneuron precursors in the olfactory bulb. Neuronal precursors cultured in Matrigel detached from chains and migrated individually in the presence of exogenously added Reelin protein or Reelin-expressing brain tissues. Furthermore, we found that in reeler mutant mice, neuronal precursors accumulated in the olfactory bulb and remained in clusters, indicating that they did not change from tangential chain-migration to radial individual migration. Our data provide direct evidence that Reelin acts as a detachment signal, but not a stop or guidance cue. We propose that Reelin may have comparable functions during development.

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Figure 1: Expression of Reelin and components of the Reelin-pathway in the OB and RMS of adult mice.
Figure 2: Exogenous Reelin induces cell dispersal of SVZ explants cultured in Matrigel.
Figure 3: Co-culture of SVZ explants with Reelin-expressing COS cell aggregates and brain tissues.
Figure 4: Morphological changes in the RMS and the OB of reeler mice.
Figure 5: Grafting of GFP-expressing neuronal precursors into wild-type and reeler RMS.

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Acknowledgements

We thank T. Curran and E. Foerster for Reelin-expressing cells, P. Durbec and G. Monti for help with the matrigel assay, G. Rougon for anti-PSA-NCAM antibody, G. Chazal for advice on immunhistochemistry and S. Alonso for Dab1 probe. We thank N. Dahmane, R. Belvindrah, P. Durbec, C. Goridis, D. Junghans and O.Pourquié for critical reading of the manuscript. This work has been supported by the Centre National de la Recherche Scientifique, Association pour la Recherche sur le Cancer and the French Ministry of Research (ACI). I.H. received a Max-Planck-Gesellschaft/CNRS fellowship.

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Correspondence to Harold Cremer.

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Hack, I., Bancila, M., Loulier, K. et al. Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis. Nat Neurosci 5, 939–945 (2002). https://doi.org/10.1038/nn923

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