Abstract
Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice—the cortical hem, the ventral pallium and the septum—from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem–derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.
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Acknowledgements
We thank M. Bonete, M. Pérez and T. Gil for technical assistance; G. D'Arcangelo (Baylor College of Medicine, Houston), J.A. Cooper (Fred Hutchinson Cancer Research Center, Seattle) and J. Raper (University of Pennsylvania, Philadelphia) for plasmids; D.R. Littmann (New York University School of Medicine, New York), J. Engele (University of Leipzig, Leipzig, Germany) and M. Goulding (Salk Institute, La Jolla, California) for Cxcr4 heterozygous mice; A. Nagy (Samuel Lunenfeld Research Institute, Toronto) for GFP mice; and S.J. Pleasure (University of California San Francisco, San Francisco) for communicating unpublished results. We are also thankful to members of the Marín lab for helpful discussions and comments. Supported by grants to O.M. from the Spanish Government (BFU2005-04773/BMC), the European Commission through the Specific Targeted Research Projects (STREP) program (contract number 005139), and the European Young Investigator (EURYI) scheme award (http://www.esf.org/euryi). V.B. is a Ramón y Cajal Investigator from the Consejo Superior de Investigaciones Científicas (CSIC) and was supported in part by the Human Frontier Science Program (HFSP). O.M. is an European Molecular Biology Organization (EMBO) Young Investigator, a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator and a EURYI Awardee.
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V.B. and O.M. planned the experiments. V.B. performed the experiments and analyzed the data. O.M. provided reagents, materials and analysis tools. V.B. and O.M. discussed the results and wrote the paper.
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Supplementary information
Supplementary Fig. 1
A model of the function of meningeal CXCL12/CXCR4 signaling on the tangential migration of hem-derived CR cells. (PDF 524 kb)
Supplementary Table 1
Qualitative classification of slice cultures in different test conditions. (PDF 52 kb)
Supplementary Table 2
Qualitative classification of hem explants according to the responses of hem-derived CR cells in confrontation assays of different test conditions. (PDF 43 kb)
Supplementary Table 3
Qualitative classification of hem explants according to the responses of hem-derived CR cells in confrontation assays of different test conditions. (PDF 61 kb)
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Borrell, V., Marín, O. Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling. Nat Neurosci 9, 1284–1293 (2006). https://doi.org/10.1038/nn1764
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DOI: https://doi.org/10.1038/nn1764
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