Abstract
Cajal-Retzius cells are critical in cortical lamination, but very little is known about their origin and development. The homeodomain transcription factor Dbx1 is expressed in restricted progenitor domains of the developing pallium: the ventral pallium (VP) and the septum. Using genetic tracing and ablation experiments in mice, we show that two subpopulations of Reelin+ Cajal-Retzius cells are generated from Dbx1-expressing progenitors. VP- and septum-derived Reelin+ neurons differ in their onset of appearance, migration routes, destination and expression of molecular markers. Together with reported data supporting the generation of Reelin+ cells in the cortical hem, our results show that Cajal-Retzius cells are generated at least at three focal sites at the borders of the developing pallium and are redistributed by tangential migration. Our data also strongly suggest that distinct Cajal-Retzius subtypes exist and that their presence in different territories of the developing cortex might contribute to region-specific properties.
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Acknowledgements
We are indebted to T.M. Jessell for having made this work possible. We thank K. Campbell for suggesting that Dbx1 progenitors give rise to Cajal-Retzius cells; M. Sunshine and D. Littman for helping in the generation of the Dbx1loxP-stop-loxP-DTA mouse line; A. Nemes and M. Mendelsohn for embryonic stem cell transfection and injection of the Dbx1Cre line; F. Tronche for providing the Nes:CRE mouse line, D. Anderson for the βactin:loxP-stop-loxP-lacZ mice and A. Goffinet for the G10 anti-Reelin monoclonal antibodies; M. Cohen-Tannoudji and F. Jaisser for the I-SceI-induced gene replacement system; P. Alexandre and R. Goiame for technical help and advice and M. Ensini, S. Garel, C. Goridis, T.M. Jessell and O. Marin for comments on the manuscript. F.B. was the recipient of a fellowship from the Académie Nationale de Médecine (France). S.A. and M.S. were supported by a grant from the Swiss National Science Foundation, by the Kanton of Basel-Stadt and by the Novartis Research Foundation. A.P. and M.W. are CNRS (Centre National de la Recherche Scientifique) Investigators. This work was supported by the Ministère de la Recherche (ACI grant # 0220575) and the Association pour la Recherche sur le Cancer (grant # 4679) to A.P.
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Supplementary information
Supplementary Fig. 1
Dbx1-derived cells are highly motile and populate preferentially rostral and caudo-ventral regions of the developing cortex up to E12.5. (PDF 19163 kb)
Supplementary Fig. 2
Temporal and spatial distribution of cell death in Dbx1DTA;Nes:Cre embryos. (PDF 27191 kb)
Supplementary Fig. 3
Novel sources of Cajal-Retzius cells and their different distribution in cortical regions. (PDF 4289 kb)
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Bielle, F., Griveau, A., Narboux-Nême, N. et al. Multiple origins of Cajal-Retzius cells at the borders of the developing pallium. Nat Neurosci 8, 1002–1012 (2005). https://doi.org/10.1038/nn1511
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DOI: https://doi.org/10.1038/nn1511
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