Skip to main content

Pioneer Neurons and Interneurons in the Developing Subplate: Molecular Markers, Cell Birthdays, and Neurotransmitters

  • Chapter
Development and Plasticity in Sensory Thalamus and Cortex

1. Abstract

Subplate neurons are essential for the development of cortical axon pathways, including thalamocortical innervation as well as the formation of some cortico-cortical and descending cortical efferent connections. Previous evidence suggests that the critical subplate neurons are early-born “pioneer” neurons, which extend the first axons out of the cortex to subcortical forebrain regions. However, pioneer neurons are not the only type of neuron in the subplate layer. The subplate contains both glutamatergic and GABAergic neurons, some of which are transitory due to either ongoing cell migration or subsequent cell death. We have studied the cellular composition of the subplate in developing mouse and human cortex by retrograde axon tracing, cell birthdating, and immunohistochemical analysis of specific markers. Our results indicate that pioneer neurons are early-born glutamatergic neurons that express transcription factor Tbr1, transgene golli-lacZ, and other markers. In contrast, GABAergic interneurons in the subplate do not make subcortical (pioneer) axon projections, but instead migrate tangentially and radially through the subplate layer, express transcription factor Dlx, and are born both early and late in corticogenesis. Subplate neurons are essential in development of the initial cortical connectivity, and it is thus important to distinguish between the different cell types present in this compartment, using molecular markers. The subplate in humans appears to contain a similar diversity of neuron types as in mice, but is markedly thicker than in mice, as confirmed by the broad band of Tbr1 expression extending below the cortical plate in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

9. References

  • Allendoerfer, K. L., Shelton, D. L., Shooter, E. M., and Shatz, C. J. (1990). Nerve growth factor receptor immunoreactivity is transiently associated with the subplate neurons of the mammalian cerebral cortex. Proc. Natl. Acad. Sci. USA 87:187–190.

    Article  PubMed  CAS  Google Scholar 

  • Allendoerfer, K. L., and Shatz, C. J. (1994). The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu. Rev. Neurosci. 17:185–218.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, S. A., Eisenstat, D. D., Shi, L., and Rubenstein, J. L. R. (1997). Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278:474–476.

    Article  PubMed  CAS  Google Scholar 

  • Antonini, A., and Shatz, C. J. (1990). Relation between putative transmitter phenotypes and connectivity of subplate neurons during cerebral cortical development. Eur. J. Neurosci. 2:744–761.

    Article  PubMed  Google Scholar 

  • Arias, M. S., Baratta, J., Yu, J., and Robertson, R. T. (2002). Absence of selectivity in the loss of neurons from the developing cortical subplate of the rat. Brain Res. Dev. Brain Res. 139:331–335.

    Article  PubMed  CAS  Google Scholar 

  • Bicknese, A. R., Sheppard, A. M., O’Leary, D. D. M., and Pearlman, A. L. (1994). Thalamocortical axons extend along a chondroitin sulfate proteoglycan-enriched pathway coincident with the neocortical subplate and distinct from the efferent path. J. Neurosci. 14:3500–3510.

    PubMed  CAS  Google Scholar 

  • Caviness, V. S., Jr. (1982). Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography. Brain Res. Dev. Brain Res. 4:293–302.

    Article  Google Scholar 

  • Chan, C.-H., Godinho, L. N., Thomaidou, D., Tan, S.-S., Gulisano, M., and Parnavelas, J. G. (2001). Emx1is a marker for pyramidal neurons of the cerebral cortex. Cereb. Cortex 11:1191–1198.

    Article  PubMed  CAS  Google Scholar 

  • Csillik, A. E., Okuno, E., Csillik, B., Knyihár, E., and Vécsei, L. (2002). Expression of kynurenine aminotransferase in the subplate of the rat and its possible role in the regulation of programmed cell death. Cereb. Cortex 12:1193–3211.

    Article  PubMed  Google Scholar 

  • Dunn, J. A., Kirsch, J. D., and Naegel, J. R. (1995). Transient immunoglobulin-like molecules are present in the subplate zone and cerebral cortex during postnatal development. Cereb. Cortex 5:494–505.

    PubMed  CAS  Google Scholar 

  • Fairén, A., Cobas, A., and Fonseca, M. (1986). Times of generation of glutamic acid decarboxylase immunoreactive neurons in mouse somatosensory cortex. J. Comp. Neurol. 251:67–83.

    Article  PubMed  Google Scholar 

  • Ferland, R. J., Cherry, T. J., Preware, P. O., Morrissey, E. E., and Walsh, C. A. (2003). Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J. Comp. Neurol. 460:266–279.

    Article  PubMed  CAS  Google Scholar 

  • Flames, N., Long, J. E., Garratt, A. N., Fischer, T. M., Gassmann, M., Birchmeier, C., Lai, C., Rubenstein, J. L. R., and Marín, O. (2004). Short-and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron 44:251–261.

    Article  PubMed  CAS  Google Scholar 

  • Ghosh, A., Antonini, A., McConnell, S. K., and Shatz, C. J. (1993). Requirement for subplate neurons in the formation of thalamocortical connections. Nature 347:179–181.

    Article  Google Scholar 

  • Ghosh, A., and Shatz, C. J. (1993). A role for subplate neurons in the patterning of connections from thalamus to neocortex. Development 117:1031–1047.

    PubMed  CAS  Google Scholar 

  • Heuer, H., Christ, S., Friedrichsen, S., Brauer, D., Winckler, M., Bauer, K., and Raivich, G. (2003). Connective tissue growth factor: a novel marker of layer VII neurons in the rat cerebral cortex. Neuroscience 119:43–52.

    Article  PubMed  CAS  Google Scholar 

  • Hevner, R. F. (2000). Development of connections in the human visual system during fetal mid-gestation: a DiI-tracing study. J. Neuropathol. Exp. Neurol. 59:385–392.

    PubMed  CAS  Google Scholar 

  • Hevner, R. F., Shi, L., Justice, N., Hsueh, Y.-P., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A. M., Campagnoni, A. T., and Rubenstein, J. L. R. (2001). Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29:353–366.

    Article  PubMed  CAS  Google Scholar 

  • Hevner, R. F., Miyashita-Lin, E., and Rubenstein, J. L. R. (2002). Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other. J. Comp. Neurol. 447:8–17.

    Article  PubMed  Google Scholar 

  • Hevner, R. F., Neogi, T., Englund, C., Daza, R. A. M., and Fink, A. (2003a). Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin. Brain Res. Dev. Brain Res. 141:39–53.

    Article  PubMed  CAS  Google Scholar 

  • Hevner, R. F., Daza, R. A. M., Rubenstein, J. L. R., Stunnenberg, H., Olavarria, J., and Englund, C. (2003b). Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons. Dev. Neurosci. 25:139–151.

    Article  PubMed  CAS  Google Scholar 

  • Hevner, R. F., Daza, R. A. M., Englund, C., Kohtz, J., and Fink, A. (2004). Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration. Neuroscience 124:605–618.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, K., Terashima, T., Nishikawa, T., and Takumi, T. (2004). Fez1 is layer-specifically expressed in the adult mouse neocortex. Eur. J. Neurosci. 20:2909–2916.

    Article  PubMed  Google Scholar 

  • Kanold, P. O., Kara, P., Reid, R. C., and Shatz, C. J. (2003). Role of subplate neurons in functional maturation of visual cortical columns. Science 301:521–525.

    Article  PubMed  CAS  Google Scholar 

  • Kostovic, I., and Judas, M. (2002). The role of the subplate zone in the structural plasticity of the developing human cerebral cortex. Neuroembryology 1:145–153.

    Article  Google Scholar 

  • Kostovic, I., and Rakic, P. (1980). Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J. Neurocytol. 9:219–242.

    Article  PubMed  CAS  Google Scholar 

  • Kostovic, I., and Rakic, P. (1990). Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain. J. Comp. Neurol. 297:441–470.

    Article  PubMed  CAS  Google Scholar 

  • Landry, C. F., Pribyl, T. M., Ellison, J. A., Givogri, M. I., Kampf, K., Campagnoni, C. W., and Campagnoni, A. T. (1998). Embryonic expression of the myelin basic protein gene: identification of a promoter region that targets transgene expression to pioneer neurons. J. Neurosci. 18:7315–7327.

    PubMed  CAS  Google Scholar 

  • Letinic, K., Zoncu, R., and Rakic, P. (2002). Origin of GABAergic neurons in the human neocortex. Nature 417:645–649.

    Article  PubMed  CAS  Google Scholar 

  • López-Bendito, G., and Molnár, Z. (2003). Thalamocortical development: how are we going to get there? Nat. Rev. Neurosci. 4:276–289.

    Article  PubMed  Google Scholar 

  • Marín, O., and Rubenstein, J. L. R. (2001). A long, remarkable journey: tangential migration in the telencephalon. Nat. Rev. Neurosci. 2:780–790.

    Article  PubMed  Google Scholar 

  • McConnell, S. K., Ghosh, A., and Shatz, C. J. (1989). Subplate neurons pioneer the first axon pathway from the cerebral cortex. Science 245:978–982.

    Article  PubMed  CAS  Google Scholar 

  • McConnell, S. K., Ghosh, A., and Shatz, C. J. (1994). Subplate pioneers and the formation of descending connections from cerebral cortex. J. Neurosci. 14:1892–1907.

    PubMed  CAS  Google Scholar 

  • McQuillen, P. S., DeFreitas, M. F., Zada, G., and Shatz, C. J. (2002). A novel role for p75NTR in subplate growth cone complexity and visual thalamocortical innervation. J. Neurosci. 22:3580–3593.

    PubMed  CAS  Google Scholar 

  • Molnár, Z., and Blakemore, C. (1995). How do thalamic axons find their way to the cortex? Trends Neurosci. 18:389–397.

    Article  PubMed  Google Scholar 

  • Molnár, Z., Adams, R., and Blakemore, C. (1998a). Mechanisms underlying the early establishment of thalamocortical connections in the rat. J. Neurosci. 18:5723–5745.

    PubMed  Google Scholar 

  • Molnár, Z., Adams, R., Goffinet, A. M., and Blakemore, C. (1998b). The role of the first postmitotic cortical cells in the development of thalamocortical innervation in the reeler mouse. J. Neurosci. 18:5746–5765.

    PubMed  Google Scholar 

  • Nery, S., Fishell, G., and Corbin, J. G. (2002). The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nat. Neurosci. 5:1279–1287.

    Article  PubMed  CAS  Google Scholar 

  • Peduzzi, J. D. (1988). Genesis of GABA-immunoreactive neurons in the ferret visual cortex. J. Neurosci. 8:920–931.

    PubMed  CAS  Google Scholar 

  • Polleux, F., Dehay, C., and Kennedy, H. (1998). Neurogenesis and commitment of corticospinal neurons in reeler. J. Neurosci. 18:9910–9923.

    PubMed  CAS  Google Scholar 

  • Rakic, S., and Zecevic, N. (2003). Emerging complexity of cortical layer I in humans. Cereb. Cortex 13:1072–1083.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Robertson, R. T., Annis, C. M., Baratta, J., Haraldson, S., Ingeman, J., Kageyama, G. H., Kimm, E., and Yu, J. (2000). Do subplate neurons comprise a transient population of cells in developing neocortex of rats? J. Comp. Neurol. 426:632–650.

    Article  PubMed  CAS  Google Scholar 

  • Sheppard, A. M., and Pearlman, A. L. (1997). Abnormal reorganization of preplate neurons and their associated extracellular matrix: an early manifestation of altered neocortical development in the reeler mutant mouse. J. Comp. Neurol. 378:173–179.

    Article  PubMed  CAS  Google Scholar 

  • Smart, I. H. M., Dehay, C., Giroud, P., Berland, M., and Kennedy, H. (2002). Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex 12:37–53.

    Article  PubMed  Google Scholar 

  • Stühmer, T., Anderson, S. A., Ekker, M., and Rubenstein, J. L. R. (2002). Expression from a Dlx gene enhancer marks adult mouse cortical GABAergic neurons. Cereb. Cortex 12:75–85.

    Article  PubMed  Google Scholar 

  • Wichterle, H., Turnbull, D. H., Nery, S., Fishell, G., and Alvarez-Buylla, A. (2001). In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128:3759–3771.

    PubMed  CAS  Google Scholar 

  • Woods, J. G., Martin, S., and Price, D. J. (1992). Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone. Brain Res. Dev. Brain Res. 66:137–140.

    Article  Google Scholar 

  • Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J. L., and Anderson, S. A. (2004). Origins of cortical interneuron subtypes. J. Neurosci. 24:2612–2622.

    Article  PubMed  CAS  Google Scholar 

  • Yuasa, S., Kitoh, J., and Kawamura, K. (1994). Interactions between growing thalamocortical afferent axons and the neocortical primordium in normal and reeler mutant mice. Anat. Embryol. 190:137–154.

    Article  PubMed  CAS  Google Scholar 

  • Zecevic, N., and Milosevic, A. (1997). The initial development of the GABA-immunoreactivity in the human cerebral cortex. J. Comp. Neurol. 380:495–506.

    Article  PubMed  CAS  Google Scholar 

  • Zecevic, N., Milosevic, A., Rakic, S., and Marin-Padilla, M. (1999). Early development and composition of the human primordial plexiform layer: an immunohistochemical study. J. Comp. Neurol. 412:241–254.

    Article  PubMed  CAS  Google Scholar 

  • Zecevic, N., Chen, Y., and Filipovic, R. (2005). Contributions of cortical subventricular zone to the development of the human cerebral cortex. J. Comp. Neurol., 491:109–122.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hevner, R.F., Zecevic, N. (2006). Pioneer Neurons and Interneurons in the Developing Subplate: Molecular Markers, Cell Birthdays, and Neurotransmitters. In: Erzurumlu, R., Guido, W., Molnár, Z. (eds) Development and Plasticity in Sensory Thalamus and Cortex. Springer, Boston, MA . https://doi.org/10.1007/978-0-387-38607-2_1

Download citation

Publish with us

Policies and ethics