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Telencephalic origin of human thalamic GABAergic neurons

Abstract

In non-primate mammalian species, telencephalic and diencephalic neurons originate from their respective local proliferative zones. Using vital dye labeling in organotypic slice cultures, we show that in human brain, a contingent of neurons from the ganglionic eminence of the telencephalon migrate to the dorsal thalamic association nuclei of the diencephalon. These neurons rely on homotypic–neurophilic guidance during their migration, are GABAergic, and express Dlx1/2 homeodomain-containing proteins. Similar experiments in a non-human primate and in rodent embryos did not reveal a similar migratory pathway. Migration assays demonstrated that the human dorsal thalamus attracts telencephalic cells, an effect not observed in the mouse, in which such migration is inhibited by chemorepulsive cues. These data suggest that modifications in the pattern of migratory guidance cues in the forebrain may underlie the appearance of a new migratory pathway and thus contribute to the evolutionary expansion of the thalamic association nuclei in the human.

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Figure 1: Localization of the GE–DT migratory stream in the fetal human forebrain.
Figure 2: Cell migration from the GE to the DT in slice cultures of human and monkey brains.
Figure 3: Neurophilic–homotypic mechanism of guidance of neurons migrating from the GE to the DT.
Figure 4: Neurons migrating from the GE to the DT are GABAergic.
Figure 5: Regulation of cell migration across the boundary between the GE and DT by long-range attractive and repulsive guidance cues.
Figure 6: Mouse DT is permissive for the migration of neurons from the GE.

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Acknowledgements

We thank J.L.R. Rubenstein and S. Anderson for providing Dlx1/2 antibodies. We thank all colleagues in P. Rakic's laboratory for their advice and comments on the manuscript.

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Correspondence to Pasko Rakic.

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Letinic, K., Rakic, P. Telencephalic origin of human thalamic GABAergic neurons. Nat Neurosci 4, 931–936 (2001). https://doi.org/10.1038/nn0901-931

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