Abstract
It is believed that postmitotic neurons migrate away from their sites of origin in the germinal zones to populate distant targets. Contrary to this notion, we found, using time-lapse imaging of brain slices, populations of neurons positioned at various levels of the developing neocortex that migrate towards the cortical ventricular zone. After a pause in this proliferative zone, they migrate radially in the direction of the pial surface to take up positions in the cortical plate. Immunohistochemical analysis together with tracer labeling in brain slices showed that cells showing ventricle-directed migration in the developing cortex are GABAergic interneurons originating in the ganglionic eminence in the ventral telencephalon. We speculate that combinations of chemoattractant and chemorepellent molecules are involved in this ventricle-directed migration and that interneurons may seek the cortical ventricular zone to receive layer information.
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References
Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex. J. Comp. Neurol. 145, 61–83 (1972).
Rakic, P. Neuronal migration and contact guidance in the primate telencephalon. Postgrad. Med. J. 54 Suppl 1, 25–40 (1978).
Angevine, J. B., Jr. & Sidman, R. L. Autoradiographic study of the cell migration during histogenesis of cerebral cortex in the mouse. Nature 192, 766–768 (1961).
Berry, M. & Rogers, A. W. The migration of neuroblasts in the developing cerebral cortex. J. Anat. 99, 691–709 (1965).
Rakic, P., Stensas, L. J., Sayre, E. & Sidman, R. L. Computer-aided three-dimensional reconstruction and quantitative analysis of cells from serial electron microscopic montages of foetal monkey brain. Nature 250, 31–34 (1974).
Hatten, M. E. Central nervous system neuronal migration. Annu. Rev. Neurosci. 22, 511–539 (1999).
O'Rourke, N. A., Dailey, M. E., Smith, S. J. & McConnell, S. K. Diverse migratory pathways in the developing cerebral cortex. Science 258, 299–302 (1992).
Tan, S. S. & Breen, S. Radial mosaicism and tangential cell dispersion both contribute to mouse neocortical development. Nature 362, 638–640 (1993).
Reid, C. B., Liang, I. & Walsh, C. Systematic widespread clonal organization in cerebral cortex. Neuron 15, 299–310 (1995).
Mione, M. C., Cavanagh, J. F., Harris, B. & Parnavelas, J. G. Cell fate specification and symmetrical/asymmetrical divisions in the developing cerebral cortex. J. Neurosci. 17, 2018–2029 (1997).
Parnavelas, J. G. The origin and migration of cortical neurones: new vistas. Trends Neurosci. 23, 126–131 (2000).
Tan, S. S. et al. Separate progenitors for radial and tangential cell dispersion during development of the cerebral neocortex. Neuron 21, 295–304 (1998).
De Carlos, J. A., Lopez-Mascaraque, L. & Valverde, F. Dynamics of cell migration from the lateral ganglionic eminence in the rat. J. Neurosci. 16, 6146–6156 (1996).
Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. L. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476 (1997).
Tamamaki, N., Fujimori, K. E. & Takauji, R. Origin and route of tangentially migrating neurons in the developing neocortical intermediate zone. J. Neurosci. 17, 8313–8323 (1997).
Lavdas, A. A., Grigoriou, M., Pachnis, V. & Parnavelas, J. G. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J. Neurosci. 19, 7881–7888 (1999).
Wichterle, H., Turnbull, D. H., Nery, S., Fishell, G., & Alvarez-Buylla, A. In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128, 3759–3771 (2001).
Anderson, S., Mione, M., Yun, K., & Rubenstein, J. L. Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb. Cortex 9, 646–654 (1999).
Denaxa, M., Chan, C.-H., Schachner, M., Parnavelas, J. G. & Karagogeos, D. The adhesion molecule TAG-1 mediates the migration of cortical interneurons from the ganglionic eminence along the corticofugal fiber system. Development 128, 4635–4644 (2001).
Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988).
McConnell, S. K. & Kaznowski, C. E. Cell cycle dependence of laminar determination in developing neocortex. Science 254, 282–285 (1991).
Nadarajah, B., Brunstrom, J. E., Grutzendler, J., Wong, R. O. L. & Pearlman, A. L. Two modes of radial migration in early development of the cerebral cortex. Nature Neurosci. 4, 143–150 (2001).
Edmondson, J. C. & Hatten, M. E. Glial-guided granule neuron migration in vitro: a high-resolution time-lapse video microscopic study. J. Neurosci. 7, 1928–1934 (1987).
Komuro, H. & Rakic, P. Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations. J. Neurosci. 15, 1110–1120 (1995).
Anderson, S. A., Marin, O., Horn, C., Jennings, K. & Rubenstein, J. L. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128, 353–363 (2001).
Luskin, M. B. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173–189 (1993).
O'Rourke, N. A., Chenn, A. & McConnell, S. K. Postmitotic neurons migrate tangentially in the cortical ventricular zone. Development 124, 997–1005 (1997).
Neyt, C., Welch, M., Langston, A., Kohtz, J. & Fishell, G. A short-range signal restricts cell movement between telencephalic proliferative zones. J. Neurosci. 17, 9194–9203 (1997).
Rakic, P. Principles of neural cell migration. Experientia 46, 882–891 (1990).
Gray, G. E., Leber, S. M. & Sanes, J. R. Migratory patterns of clonally related cells in the developing central nervous system. Experientia 46, 929–940 (1990).
Miller, M. W. Cogeneration of retrogradely labeled corticocortical projection and GABA-immunoreactive local circuit neurons in cerebral cortex. Dev. Brain Res. 23, 187–192 (1985).
Cavanagh, M. E. & Parnavelas, J. G. Development of somatostatin immunoreactive neurons in the rat occipital cortex: a combined immunocytochemical–autoradiographic study. J. Comp. Neurol. 268, 1–12 (1988).
Acknowledgements
The work was supported by grants by the Wellcome Trust to B.N. and J.G.P. (grant number 050325) and by the US National Eye Institute to R.O.L.W.
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Nadarajah, B., Alifragis, P., Wong, R. et al. Ventricle-directed migration in the developing cerebral cortex. Nat Neurosci 5, 218–224 (2002). https://doi.org/10.1038/nn813
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DOI: https://doi.org/10.1038/nn813
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