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  • Review Article
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A long, remarkable journey: Tangential migration in the telencephalon

Nature Reviews Neuroscience volume 2, pages 780–790 (2001)Cite this article

Key Points

  • In the developing central nervous system (CNS), most neurons migrate from the site of their last mitotic division, near the ventricle, towards the outer surface, where they integrate into specific circuits. In the telencephalon, radial migration is recognized as the primary mechanism by which developing neurons reach their final position in the cortex, but there is growing evidence that some neurons migrate tangentially. The subpallial telencephalon seems to generate oligodendrocytes and GABA (γ-aminobutyric acid)-expressing interneurons with tangential migratory properties.

  • Other tangential migratory routes have been described in the telencephalon. For example, some progenitor cells in the telencephalic subventricular zone continue to proliferate in the adult brain, and they migrate in the rostral migratory stream (RMS) to the olfactory bulb to generate granule and periglomerular cells. Striatal GABA-expressing and cholinergic interneurons also migrate tangentially within the telencephalon.

  • Recent studies indicate that cells that migrate tangentially to the cortex originate in multiple regions of the subpallial telencephalon, including the lateral and medial ganglionic eminences (LGE and MGE), the anterior entopeduncular area (AEP) and possibly the retrobulbar area. Three partially overlapping temporal phases of migration can be distinguished.

  • Examining the distribution of interneurons in mice lacking transcription factors such as Nkx2.1, Pax6 and Gsh2, which regulate regional specification in the subpallial telencephalon, has clarified the anatomical origins of different migratory streams. Reduced numbers of MGE and AEP progenitor cells lead to fewer cortical GABA-expressing interneurons, whereas reduced numbers of dorsal LGE progenitors lead to lower numbers of olfactory bulb interneurons.

  • Several transcription factors have been identified that are essential for the differentiation of tangentially migrating interneurons, including Dlx1, Dlx2 and Mash1. Analysis of the distribution of interneurons in mice lacking these factors has revealed that they are essential regulators of the timing of interneuron production and differentiation.

  • At least three different types of factor regulate tangential migration: motogenic factors that stimulate the movement of cells, factors that constitute the extracellular substrate for their migration, and factors that guide different migratory streams through appropriate pathways towards their targets.

  • Migrating neuroblasts in the adult RMS move in tightly associated chains, indicating that this type of migration is regulated by cues that act by cell–cell contacts.

  • Tangential migration in the telencephalon, and perhaps in other regions of the CNS, might be a mechanism selected through evolution to increase the cellular complexity of specific circuits, such as those of the cerebral cortex.

Abstract

Recent studies on the origin of cell populations in rodent and chicken embryonic brains provide evidence for extensive tangential migration within the developing telencephalon. On the basis of these findings, a new concept of corticogenesis has emerged, which proposes that two distinct neuronal populations cooperate in the formation of the cortex. One population consists of radially migrating neurons that originate in the ventricular zone of the pallium (cortex) and give rise to the glutamatergic pyramidal neurons. The second population consists of tangentially migrating neurons that originate in the ventricular zone of the subpallium (subcortical telencephalon) and give rise to GABA (γ-aminobutyric acid)-producing local circuit neurons. The subpallium is also the origin of other cell types that follow distinct tangential trajectories to migrate to structures such as the olfactory bulb and the striatum. Here, we review evidence that supports the existence of several tangential migration pathways in the telencephalon, and summarize recent findings that describe their regulation.

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Figure 1: Streams of tangentially migrating interneurons from the subpallial telencephalon.
Figure 2: Routes of tangential migration of immature interneurons from the subpallial telencephalon to the cortex.
Figure 3: Interactions between regulatory genes contribute to the generation of subpallial progenitor domains in the telencephalon.
Figure 4: Neuropilin receptors regulate the sorting of striatal and cortical interneurons.
Figure 5: Coordination of patterning and migration mechanisms is required to achieve the cellular complexity of the telencephalon.

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References

  1. Angevine, J. B. & Sidman, R. L. Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse. Nature 192, 766–768 (1961).

    Article  PubMed  Google Scholar 

  2. Marín-Padilla, M. Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis domestica). A Golgi study. I. The primordial neocortical organization. Z. Anat. Entwicklungsgesch. 134, 117–145 (1971).

    Article  PubMed  Google Scholar 

  3. Rakic, P. Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science 183, 425–427 (1974).

    Article  CAS  PubMed  Google Scholar 

  4. Nadarajah, B., Brunstrom, J. E., Grutzendler, J., Wong, R. O. & Pearlman, A. L. Two modes of radial migration in early development of the cerebral cortex. Nature Neurosci. 4, 143–150 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Hatten, M. E. Central nervous system neuronal migration. Annu. Rev. Neurosci. 22, 511–539 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Rice, D. S. & Curran, T. Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS. Genes Dev. 13, 2758–2773 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Gleeson, J. G. & Walsh, C. A. Neuronal migration disorders: from genetic diseases to developmental mechanisms. Trends Neurosci. 23, 352–359 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Rakic, P. Molecular and cellular mechanisms of neuronal migration: relevance to cortical epilepsies. Adv. Neurol. 84, 1–14 (2000).

    CAS  PubMed  Google Scholar 

  9. Walsh, C. A. Genetics of neuronal migration in the cerebral cortex. Ment. Retard. Dev. Disabil. Res. Rev. 6, 34–40 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Rice, D. S. & Curran, T. Role of the reelin signaling pathway in central nervous system development. Annu. Rev. Neurosci. 24, 1005–1039 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Ross, M. E. & Walsh, C. A. Human brain malformations and their lessons for neuronal migration. Annu. Rev. Neurosci. 24, 1041–1070 (2001).References 5–11 review research that addresses the developmental mechanisms underlying radial migration in normal and mutant cortex.

    Article  CAS  PubMed  Google Scholar 

  12. Morest, D. K. A study of neurogenesis in the forebrain of opossum pouch young. Z. Anat. Entwicklungsgesch. 130, 265–305 (1970).

    Article  CAS  PubMed  Google Scholar 

  13. Rakic, P. Guidance of neurons migrating to the fetal monkey neocortex. Brain Res. 33, 471–476 (1971).

    Article  CAS  PubMed  Google Scholar 

  14. Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex. J. Comp. Neurol. 145, 61–83 (1972).

    Article  CAS  PubMed  Google Scholar 

  15. 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).

    Article  CAS  PubMed  Google Scholar 

  16. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Misson, J. P., Austin, C. P., Takahashi, T., Cepko, C. L. & Caviness, V. S. Jr. The alignment of migrating neural cells in relation to the murine neopallial radial glial fiber system. Cereb. Cortex 1, 221–229 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Komuro, H. & Rakic, P. Modulation of neuronal migration by NMDA receptors. Science 260, 95–97 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Stensaas, L. J. The development of hippocampal and dorsolateral pallial regions of the cerebral hemisphere in fetal rabbits. IV. Forty-one millimeter stage, intermediate lamina. J. Comp. Neurol. 131, 409–422 (1967).

    Article  CAS  PubMed  Google Scholar 

  20. Shoukimas, G. M. & Hinds, J. W. The development of the cerebral cortex in the embryonic mouse: an electron microscopic serial section analysis. J. Comp. Neurol. 179, 795–830 (1978).

    Article  CAS  PubMed  Google Scholar 

  21. Price, J. & Thurlow, L. Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. Development 104, 473–482 (1988).

    CAS  PubMed  Google Scholar 

  22. Walsh, C. & Cepko, C. L. Clonally related cortical cells show several migration patterns. Science 241, 1342–1345 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. Austin, C. P. & Cepko, C. L. Cellular migration patterns in the developing mouse cerebral cortex. Development 110, 713–732 (1990).

    CAS  PubMed  Google Scholar 

  24. Walsh, C. & Cepko, C. L. Widespread dispersion of neuronal clones across functional regions of the cerebral cortex. Science 255, 434–440 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Reid, C. B., Liang, I. & Walsh, C. Systematic widespread clonal organization in cerebral cortex. Neuron 15, 299–310 (1995).References 22–25 provide evidence that some clonally related neurons in the cerebral cortex disperse tangentially across functionally different areas of the cortex.

    Article  CAS  PubMed  Google Scholar 

  26. 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).

    Article  CAS  PubMed  Google Scholar 

  27. Tan, S. S. & Breen, S. Radial mosaicism and tangential cell dispersion both contribute to mouse neocortical development. Nature 362, 638–640 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Tan, S. S. et al. Cell dispersion patterns in different cortical regions studied with an X-inactivated transgenic marker. Development 121, 1029–1039 (1995).Using X-inactivation mosaics, the studies described in references 27 and 28 provided evidence that some cortical neurons disperse tangentially in the cerebral cortex.

    CAS  PubMed  Google Scholar 

  29. Mione, M. C., Cavanagh, J. F. R., Harris, B. & Parnavelas, J. G. Cell fate specification and symmetrical/asymmetrical divisions in the developing cerebral cortex. J. Neurosci. 17, 2018–2029 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tan, S. S. et al. Separate progenitors for radial and tangential cell dispersion during development of the cerebral neocortex. Neuron 21, 295–304 (1998).Showed that radially dispersed neurons in the cortex express glutamate, whereas tangential progenitors are predominantly GABA producing.

    Article  CAS  PubMed  Google Scholar 

  31. Porteus, M. H. et al. DLX-2, MASH-1, and MAP-2 expression and bromodeoxyuridine incorporation define molecularly distinct cell populations in the embryonic mouse forebrain. J. Neurosci. 14, 6370–6383 (1994).First indicated that Dlx2-positive cells might migrate tangentially from the subpallium to the cortex and olfactory bulb.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. De Carlos, J. A., López-Mascaraque, L. & Valverde, F. Dynamics of cell migration from the lateral ganglionic eminence in the rat. J. Neurosci. 16, 6146–6156 (1996).The first evidence that cells derived from the subpallium migrate tangentially into the cortex. Using different methods, experiments described in references 32 and 33 gave similar results.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. L. R. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476 (1997).In addition to providing evidence for the existence of a tangential migration from the subpallium to the cortex, this is the first paper to show that cortical GABA interneurons originate in the subpallial telencephalon and that their development is largely dependent on Dlx genes.

    Article  CAS  PubMed  Google Scholar 

  34. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Van Eden, C. G., Mrzljak, L., Voorn, P. & Uylings, H. B. Prenatal development of GABA-ergic neurons in the neocortex of the rat. J. Comp. Neurol. 289, 213–227 (1989).

    Article  CAS  PubMed  Google Scholar 

  36. DeDiego, I., Smith-Fernández, A. & Fairén, A. Cortical cells that migrate beyond area boundaries: characterization of an early neuronal population in the lower intermediate zone of prenatal rats. Eur. J. Neurosci. 6, 983–997 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sussel, L., Marín, O., Kimura, S. & Rubenstein, J. L. R. Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development 126, 3359–3370 (1999).

    CAS  PubMed  Google Scholar 

  39. Wichterle, H., Garcia-Verdugo, J. M., Herrera, D. G. & Alvarez-Buylla, A. Young neurons from medial ganglionic eminence disperse in adult and embryonic brain. Nature Neurosci. 2, 461–466 (1999).Using different methods, references 37–39 showed that the MGE is a source of GABA neurons that migrate tangentially to the cortex.

    Article  CAS  PubMed  Google Scholar 

  40. Marín, O., Yaron, A., Bagri, A., Tessier-Lavigne, M. & Rubenstein, J. L. R. Sorting of striatal and cortical interneurons regulated by semaphorin/neuropilin interactions. Science 293, 872–875 (2001).Describes a novel mechanism that regulates the segregation of cortical and striatal interneurons during development, and identifies a role for neuropilin receptors in this process.

    Article  PubMed  Google Scholar 

  41. Pleasure, S. J. et al. Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Neuron 28, 727–740 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Casarosa, S., Fode, C. & Guillemot, F. Mash1 regulates neurogenesis in the ventral telencephalon. Development 126, 525–534 (1999).

    CAS  PubMed  Google Scholar 

  43. Horton, S., Meredith, A., Richardson, J. A. & Johnson, J. E. Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1. Mol. Cell. Neurosci. 14, 355–369 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Wichterle, H., Turnbull, D. H., Nery, S., Fishell, G. & Alvarez-Buylla, A. In utero fate mapping reveals distinct neuronal migratory pathways in mammalian forebrain. Development (in the press).References 44 and 45 provide the first clear evidence that cells derived from the subpallium ultimately constitute a stable population of interneurons in the adult cortex.

  45. Cobos, I., Puelles, L. & Martínez, S. The avian telencephalic subpallium originates inhibitory neurons that invade tangentially the pallium (dorsal ventricular ridge and cortical areas). Dev. Biol. (in the press).

  46. Zerucha, T. et al. A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain. J. Neurosci. 20, 709–721 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Stühmer, T., Puelles, L., Ekker, M. & Rubenstein, J. L. R. Expression from a Dlx gene enhancer marks adult mouse cortical GABAergic neurons. Cereb. Cortex (in the press).

  48. Spassky, N. et al. Multiple restricted origin of oligodendrocytes. J. Neurosci. 18, 8331–8343 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Olivier, C. et al. Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo. Development 128, 1757–1769 (2001).

    CAS  PubMed  Google Scholar 

  50. Shimada, M. Cytokinetics and histogenesis of early postnatal mouse brain as studied by 3H-thymidine autoradiography. Arch. Histol. Jpn. 26, 413–437 (1966).

    Article  CAS  PubMed  Google Scholar 

  51. Hinds, J. W. Autoradiographic study of histogenesis in the mouse olfactory bulb. I. Time of origin of neurons and neuroglia. J. Comp. Neurol. 134, 287–304 (1968).

    Article  CAS  PubMed  Google Scholar 

  52. Hinds, J. W. Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration. J. Comp. Neurol. 134, 305–322 (1968).

    Article  CAS  PubMed  Google Scholar 

  53. Altman, J. Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J. Comp. Neurol. 137, 433–457 (1969).

    Article  CAS  PubMed  Google Scholar 

  54. Bayer, S. A. 3H-thymidine-radiographic studies of neurogenesis in the rat olfactory bulb. Exp. Brain Res. 50, 329–340 (1983).

    CAS  PubMed  Google Scholar 

  55. Kishi, K. Golgi studies on the development of granule cells of the rat olfactory bulb with reference to migration in the subependymal layer. J. Comp. Neurol. 258, 112–124 (1987).

    Article  CAS  PubMed  Google Scholar 

  56. Luskin, M. B. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173–189 (1993).

    Article  CAS  PubMed  Google Scholar 

  57. Lois, C. & Alvarez-Buylla, A. Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145–1148 (1994).Using different approaches, references 56 and 57 first showed a migratory pathway from the anterior SVZ to the olfactory bulb.

    Article  CAS  PubMed  Google Scholar 

  58. Kornack, D. R. & Rakic, P. The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc. Natl Acad. Sci. USA 98, 4752–4757 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Marín, O., Anderson, S. A. & Rubenstein, J. L. R. Origin and molecular specification of striatal interneurons. J. Neurosci. 20, 6063–6076 (2000).Presents evidence that most striatal interneurons arise through tangential migration from more ventral regions of the subpallium.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Sidman, R. L. & Rakic, P. Neuronal migration, with special reference to developing human brain: a review. Brain Res. 62, 1–35 (1973).A classic review of neuronal migration in the CNS.

    Article  CAS  PubMed  Google Scholar 

  61. Letinic, K. & Rakic, P. Telencephalic origin of human thalamic GABAergic neurons. Nature Neurosci. 4, 860–862 (2001).

    Article  Google Scholar 

  62. Meyer, G., Soria, J. M., Martínez-Galán, J. R., Martín-Clemente, B. & Fairén, A. Different origins and developmental histories of transient neurons in the marginal zone of the fetal and neonatal rat cortex. J. Comp. Neurol. 397, 493–518 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Anderson, S. A., Marín, O., Horn, C., Jennings, K. & Rubenstein, J. L. R. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128, 353–363 (2001).The first paper to show that cells derived from distinct progenitor zones in the subpallium follow spatially and temporally different routes in their migration to the cortex. With reference 41 , provided evidence that different cortical interneuron subclasses come from different progenitor domains.

    CAS  PubMed  Google Scholar 

  64. Nery, S., Wichterle, H. & Fishell, G. Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development 128, 527–540 (2001).

    CAS  PubMed  Google Scholar 

  65. Tekki-Kessaris, N. et al. Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development 128, 2545–2554 (2001).

    CAS  PubMed  Google Scholar 

  66. Stoykova, A., Treichel, D., Hallonet, M. & Gruss, P. Pax6 modulates the dorsoventral patterning of the mammalian telencephalon. J. Neurosci. 20, 8042–8050 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Toresson, H., Potter, S. S. & Campbell, K. Genetic control of dorsal–ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Development 127, 4361–4371 (2000).

    CAS  PubMed  Google Scholar 

  68. Corbin, J. G., Gaiano, N., Machold, R. P., Langston, A. & Fishell, G. The Gsh2 homeodomain gene controls multiple aspects of telencephalic development. Development 127, 5007–5020 (2000).

    CAS  PubMed  Google Scholar 

  69. Yun, K., Potter, S. & Rubenstein, J. L. R. Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon. Development 128, 193–205 (2001).Together with reference 38 , references 66–69 describe the role of several transcription factors in the establishment of different progenitor zones in the telencephalon.

    CAS  PubMed  Google Scholar 

  70. Chapouton, P., Gärtner, A. & Götz, M. The role of Pax6 in restricting cell migration between developing cortex and basal ganglia. Development 126, 5569–5579 (1999).

    CAS  PubMed  Google Scholar 

  71. Dellovade, T. L., Pfaff, D. W. & Schwanzel-Fukuda, M. Olfactory bulb development is altered in small-eye (Sey) mice. J. Comp. Neurol. 402, 402–418 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Van der Kooy, D. & Fishell, G. Neuronal birthdate underlies the development of striatal compartments. Brain Res. 401, 155–161 (1987).

    Article  CAS  PubMed  Google Scholar 

  73. Anderson, S., Mione, M., Yun, K. & Rubenstein, J. L. R. Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb. Cortex 9, 646–654 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Hevner, R. F. et al. Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29, 353–366 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Cecchi, C. & Boncinelli, E. Emx homeogenes and mouse brain development. Trends Neurosci. 23, 347–352 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Bulfone, A. et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron 21, 1273–1282 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Iwasato, T. et al. Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406, 726–731 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Puelles, L. et al. Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1. J. Comp. Neurol. 424, 409–438 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Nieto, M., Schuurmans, C., Britz, O. & Guillemot, F. Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors. Neuron 29, 401–413 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Fode, C. et al. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 14, 67–80 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Porteus, M. H., Bulfone, A., Ciaranello, R. D. & Rubenstein, J. L. R. Isolation and characterization of a novel cDNA clone encoding a homeodomain that is developmentally regulated in the ventral forebrain. Neuron 7, 221–229 (1991).

    Article  CAS  PubMed  Google Scholar 

  82. Price, M., Lemaistre, M., Pischetola, M., Di Lauro, R. & Duboule, D. A mouse gene related to Distal-less shows a restricted expression in the developing forebrain. Nature 351, 748–751 (1991).

    Article  CAS  PubMed  Google Scholar 

  83. Robinson, G. W., Wray, S. & Mahon, K. A. Spatially restricted expression of a member of a new family of murine Distal-less homeobox genes in the developing forebrain. New Biol. 3, 1183–1194 (1991).

    CAS  PubMed  Google Scholar 

  84. Lo, L. C., Johnson, J. E., Wuenschell, C. W., Saito, T. & Anderson, D. J. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. Genes Dev. 5, 1524–1537 (1991).

    Article  CAS  PubMed  Google Scholar 

  85. Bulfone, A. et al. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J. Neurosci. 13, 3155–3172 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Guillemot, F. & Joyner, A. L. Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. Mech. Dev. 42, 171–185 (1993).

    Article  CAS  PubMed  Google Scholar 

  87. Eisenstat, D. D. et al. DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. J. Comp. Neurol. 414, 217–237 (1999).

    Article  CAS  PubMed  Google Scholar 

  88. Anderson, S. A. et al. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron 19, 27–37 (1997).

    Article  CAS  PubMed  Google Scholar 

  89. Liu, J. K., Ghattas, I., Liu, S., Chen, S. & Rubenstein, J. L. R. Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Dev. Dyn. 210, 498–512 (1997).

    Article  CAS  PubMed  Google Scholar 

  90. Powell, E. M., Mars, W. M. & Levitt, P. Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon. Neuron 30, 79–89 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Brunstrom, J. E., Gray-Swain, M. R., Osborne, P. A. & Pearlman, A. L. Neuronal heterotopias in the developing cerebral cortex produced by neurotrophin-4. Neuron 18, 505–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  92. Behar, T. N. et al. Neurotrophins stimulate chemotaxis of embryonic cortical neurons. Eur. J. Neurosci. 9, 2561–2570 (1997).

    Article  CAS  PubMed  Google Scholar 

  93. O'Rourke, N. A., Sullivan, D. P., Kaznowski, C. E., Jacobs, A. A. & McConnell, S. K. Tangential migration of neurons in the developing cerebral cortex. Development 121, 2165–2176 (1995).

    CAS  PubMed  Google Scholar 

  94. Métin, C. & Godement, P. The ganglionic eminence may be an intermediate target for corticofugal and thalamocortical axons. J. Neurosci. 16, 3219–3235 (1996).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Métin, C., Denizot, J. P. & Ropert, N. Intermediate zone cells express calcium-permeable AMPA receptors and establish close contact with growing axons. J. Neurosci. 20, 696–708 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  96. 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 (in the press).Indicates a role for the adhesion molecule TAG-1 in regulating the migration of tangentially migrating neurons in the telencephalon.

  97. Yoshida, K., Tobet, S. A., Crandall, J. E., Jimenez, T. P. & Schwarting, G. A. The migration of luteinizing hormone-releasing hormone neurons in the developing rat is associated with a transient, caudal projection of the vomeronasal nerve. J. Neurosci. 15, 7769–7777 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Parnavelas, J. G. The origin and migration of cortical neurones: new vistas. Trends Neurosci. 23, 126–131 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Giger, R. J., Wolfer, D. P., De Wit, G. M. & Verhaagen, J. Anatomy of rat semaphorin III/collapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis. J. Comp. Neurol. 375, 378–392 (1996).

    Article  CAS  PubMed  Google Scholar 

  100. Serafini, T. et al. Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 87, 1001–1014 (1996).

    Article  CAS  PubMed  Google Scholar 

  101. Livesey, F. J. & Hunt, S. P. Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development. Mol. Cell. Neurosci. 8, 417–429 (1997).

    Article  CAS  PubMed  Google Scholar 

  102. Skaliora, I., Singer, W., Betz, H. & Püschel, A. W. Differential patterns of semaphorin expression in the developing rat brain. Eur. J. Neurosci. 10, 1215–1229 (1998).

    Article  CAS  PubMed  Google Scholar 

  103. De Castro, F., Hu, L., Drabkin, H., Sotelo, C. & Chédotal, A. Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted semaphorins. J. Neurosci. 19, 4428–4436 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Yuan, W. et al. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev. Biol. 212, 290–306 (1999).

    Article  CAS  PubMed  Google Scholar 

  105. Hamasaki, T., Goto, S., Nishikawa, S. & Ushio, Y. A role of netrin-1 in the formation of the subcortical structure striatum: repulsive action on the migration of late-born striatal neurons. J. Neurosci. 21, 4271–4280 (2001).

    Article  Google Scholar 

  106. Brose, K. & Tessier-Lavigne, M. Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr. Opin. Neurobiol. 10, 95–102 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Hu, H. Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23, 703–711 (1999).

    Article  CAS  PubMed  Google Scholar 

  108. Wu, W. et al. Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 400, 331–336 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Zhu, Y., Li, H., Zhou, L., Wu, J. Y. & Rao, Y. Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex. Neuron 23, 473–485 (1999).

    Article  CAS  PubMed  Google Scholar 

  110. Chen, J. H., Wen, L., Dupuis, S., Wu, J. Y. & Rao, Y. The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons. J. Neurosci. 21, 1548–1556 (2001).References 107–110 showed that cells derived from the subpallium are repelled by Slit proteins in vitro.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Raper, J. A. Semaphorins and their receptors in vertebrates and invertebrates. Curr. Opin. Neurobiol. 10, 88–94 (2000).

    Article  CAS  PubMed  Google Scholar 

  112. Tamagnone, L. & Comoglio, P. M. Signalling by semaphorin receptors: cell guidance and beyond. Trends Cell Biol. 10, 377–383 (2000).

    Article  CAS  PubMed  Google Scholar 

  113. Lois, C., García-Verdugo, J. M. & Alvarez-Buylla, A. Chain migration of neuronal precursors. Science 271, 978–981 (1996).Identifies a new mechanism of neuronal migration in the telencephalon.

    Article  CAS  PubMed  Google Scholar 

  114. Wichterle, H., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Direct evidence for homotypic, glia-independent neuronal migration. Neuron 18, 779–791 (1997).

    Article  CAS  PubMed  Google Scholar 

  115. Bonfanti, L. & Theodosis, D. T. Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb. Neuroscience 62, 291–305 (1994).

    Article  CAS  PubMed  Google Scholar 

  116. Rousselot, P., Lois, C. & Alvarez-Buylla, A. Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice. J. Comp. Neurol. 351, 51–61 (1995).

    Article  CAS  PubMed  Google Scholar 

  117. Jankovski, A. & Sotelo, C. Subventricular zone–olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation. J. Comp. Neurol. 371, 376–396 (1996).

    Article  CAS  PubMed  Google Scholar 

  118. Tomasiewicz, H. et al. Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system. Neuron 11, 1163–1174 (1993).

    Article  CAS  PubMed  Google Scholar 

  119. Cremer, H. et al. Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367, 455–459 (1994).

    Article  CAS  PubMed  Google Scholar 

  120. Ono, K., Tomasiewicz, H., Magnuson, T. & Rutishauser, U. N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13, 595–609 (1994).

    Article  CAS  PubMed  Google Scholar 

  121. Hu, H., Tomasiewicz, H., Magnuson, T. & Rutishauser, U. The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron 16, 735–743 (1996).

    Article  CAS  PubMed  Google Scholar 

  122. Conover, J. C. et al. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nature Neurosci. 3, 1091–1097 (2000).

    Article  CAS  PubMed  Google Scholar 

  123. Marín, O. & Rubenstein, J. L. R. in Mouse Development. Patterning, Morphogenesis, and Organogenesis (eds Rossant, J. & Tam, P. P. L.) (Academic, San Diego, 2001).A recent review of the literature on forebrain development.

    Google Scholar 

  124. Shimamura, K. & Rubenstein, J. L. R. Inductive interactions direct early regionalization of the mouse forebrain. Development 124, 2709–2718 (1997).

    CAS  PubMed  Google Scholar 

  125. López-Coviella, I., Berse, B., Krauss, R., Thies, R. S. & Blusztajn, J. K. Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 289, 313–316 (2000).

    Article  PubMed  Google Scholar 

  126. Striedter, G. F., Marchant, T. A. & Beydler, S. The 'neostriatum' develops as part of the lateral pallium in birds. J. Neurosci. 18, 5839–5849 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Hamasaki, T., Goto, S., Nishikawa, S. & Ushio, Y. Early-generated preplate neurons in the developing telencephalon: inward migration into the developing striatum. Cereb. Cortex 11, 474–484 (2001).

    Article  CAS  PubMed  Google Scholar 

  128. Alcántara, S., Ruiz, M., De Castro, F., Soriano, E. & Sotelo, C. Netrin 1 acts as an attractive or as a repulsive cue for distinct migrating neurons during the development of the cerebellar system. Development 127, 1359–1372 (2000).

    PubMed  Google Scholar 

  129. Bloch-Gallego, E., Ezan, F., Tessier-Lavigne, M. & Sotelo, C. Floor plate and netrin-1 are involved in the migration and survival of inferior olivary neurons. J. Neurosci. 19, 4407–4420 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ono, K. & Kawamura, K. Mode of neuronal migration of the pontine stream in fetal mice. Anat. Embryol. (Berl.) 182, 11–19 (1990).

    Article  CAS  Google Scholar 

  131. Yee, K. T., Simon, H. H., Tessier-Lavigne, M. & O'Leary, D. M. Extension of long leading processes and neuronal migration in the mammalian brain directed by the chemoattractant netrin-1. Neuron 24, 607–622 (1999).

    Article  CAS  PubMed  Google Scholar 

  132. Kawaguchi, Y., Wilson, C. J., Augood, S. J. & Emson, P. C. Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci. 18, 527–535 (1995).

    Article  CAS  PubMed  Google Scholar 

  133. Freund, T. F. & Buzsáki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996).

    Article  CAS  PubMed  Google Scholar 

  134. Kawaguchi, Y. & Kubota, Y. GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb. Cortex 7, 476–486 (1997).

    Article  CAS  PubMed  Google Scholar 

  135. DeFelipe, J. Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28K, parvalbumin and calretinin in the neocortex. J. Chem. Neuroanat. 14, 1–19 (1997).

    Article  CAS  PubMed  Google Scholar 

  136. McBain, C. J. & Fisahn, A. Interneurons unbound. Nature Rev. Neurosci. 2, 11–23 (2001).

    Article  CAS  Google Scholar 

  137. Gall, C. M., Hendry, S. H., Seroogy, K. B., Jones, E. G. & Haycock, J. W. Evidence for coexistence of GABA and dopamine in neurons of the rat olfactory bulb. J. Comp. Neurol. 266, 307–318 (1987).

    Article  CAS  PubMed  Google Scholar 

  138. Del Rio, J. A., Soriano, E. & Ferrer, I. Development of GABA-immunoreactivity in the neocortex of the mouse. J. Comp. Neurol. 326, 501–526 (1992).

    Article  CAS  PubMed  Google Scholar 

  139. Rakic, P. Defects of neuronal migration and the pathogenesis of cortical malformations. Prog. Brain Res. 73, 15–37 (1988).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank A. Alvarez-Buylla, S. Pleasure, B. Rico and A. Bagri for comments and suggestions. Research in the laboratory of J.L.R.R. is supported by the Nina Ireland Laboratory, the National Institute on Drug Abuse and the National Institute of Mental Health. O.M. is the recipient of a National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award and is a University of California, Davis, Medical Investigation of Neurodevelopmental Disorders (MIND) Institute Scholar.

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Authors and Affiliations

  1. Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, Langley Porter Psychiatric Institute, 401 Parnassus Avenue

    Oscar Marín & John L. R. Rubenstein

  2. University of California, San Francisco, 94143-0984, California, USA

    Oscar Marín & John L. R. Rubenstein

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  1. Oscar Marín
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Correspondence to John L. R. Rubenstein.

Related links

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DATABASE

LocusLink

BDNF

Bmp4

Bmp9

calbindin

calretinin

Dcc

Dlx1

Dlx2

Dlx5

Dlx6

Emx1

EphB

ephrin-B2

Fgf8

Gsh2

HGF/SF

Lhx6

Lhx7

Mash1

netrin

neuropeptide Y

neuropilin 1

neuropilin 2

Nkx2.1

NT4

parvalbumin

Pax6

PSA-NCAM

Robo

Sema3a

Sema3f

Shh

Slit

TAG-1

Tbr1

TrkB

uPAR

Wnt3a

Glossary

SOMAL DISPLACEMENT

Displacement of the cell body, as opposed to migration of the whole cell. Also known as somal translocation.

X-INACTIVATED TRANSGENIC MOSAICS

Based on the process of X-linked gene inactivation, the analysis of X-linked transgenic markers (e.g. LacZ) provides a method to distinguish between clonally related cell populations in the developing brain.

PALLIUM

The roof of the telencephalon. It contains both cortical structures (e.g. hippocampus and neocortex) and deep-lying nuclear structures (e.g. claustrum and parts of the amygdala). Pallium is not synonymous with cortex.

SUBPALLIUM

The base of the telencephalon. It consists primarily of the basal ganglia; for example, the striatum, globus pallidus, and parts of the septum and amygdala.

STRIATUM

Part of the subpallium and one of the components of the striatopallidal complex. It comprises deep (caudate nucleus, putamen and nucleus accumbens) and superficial (olfactory tubercle) parts.

DII

DiI is a lipophilic carbocyanine dye that emits an intense fluorescence when incorporated into cell membranes. It is commonly used to track cell migration, or for the retrograde or anterograde tracing of axons. It can be used on both live and fixed tissue.

HOMEOBOX

A sequence of about 180 base pairs that encodes a DNA-binding protein sequence known as the homeodomain.

CRE RECOMBINASE

Part of a site-specific recombination system derived from Escherichia coli bacteriophage P1. Two short DNA sequences (loxP sites) are engineered to flank the target DNA. Activation of the Cre recombinase enzyme catalyses recombination between the loxP sites, leading to excision of the intervening sequence.

BASIC HELIX–LOOP–HELIX

A structural motif present in many transcription factors, which is characterized by two α-helices separated by a loop. The helices mediate dimerization, and the adjacent basic region is required for DNA binding.

CORTICOFUGAL AXONS

Generic term to define efferent projections from the cerebral cortex.

RECEPTOR TYROSINE KINASES

A family of membrane receptors, the intracellular domains of which catalyse the phosphorylation, by ATP, of specific tyrosine residues on their target proteins.

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Marín, O., Rubenstein, J. A long, remarkable journey: Tangential migration in the telencephalon. Nat Rev Neurosci 2, 780–790 (2001). https://doi.org/10.1038/35097509

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