Postnatal Expression of Doublecortin (Dcx) in the Developing Cerebellar Cortex of Mouse

Abstract

We have investigated the expression of Doublecortin (Dcx) protein in the developing cerebellum of mouse from postnatal 2nd day to postnatal 22nd day and in young adults by immunohistochemistry. Strong expression of Dcx was present in the inner zone of the external granule cell layer, and remained strong while postmitotic granule cell precursors were present in this transitory layer. Descending granule cell precursors exhibited Dcx immunostaining not only while migrating but for a short time also after their settlement. Dcx-immunostained cells appeared in deep cerebellocortical territories and in the cerebellar white matter during the first postnatal week. These bipolar cells were arranged in the sagittal plane and built up transitory migratory streams during the second postnatal week and their number gradually decreased during the third postnatal week. Upward migration of bipolar cells was observed while leaving the migratory streams, penetrating the internal granule cell layer and the molecular layer. These cells were considered as precursors of late migrating molecular layer interneurons. However, a proportion of Dcx-immunostained cells underwent a bipolar-to-multipolar dendritic remodellation and — on the basis of strong morphological similarities — was taken for “multipotent progenitor cells”, described recently in the neocortex of adult rat.

References

  1. 1.

    Altman, J. (1972) Postnatal development of the cerebellar cortex in the rat. III. Maturation of the components of the granular layer. J. Comp. Neurol. 145, 465–514.

    CAS  Article  Google Scholar 

  2. 2.

    Altman, J., Bayer, S. A. (1997) Development of the Cerebellar System in Relation to Its Evolution, Structure, and Functions. CRC Press, Boca Raton.

    Google Scholar 

  3. 3.

    Book, K. J., Morest, D. K. (1990) Migration of neuroblasts by perikaryal translocation: role of cellular elongation and axonal outgrowth in the acoustic nuclei of the chick embryo medulla. J. Comp. Neurol. 297, 55–76.

    CAS  Article  Google Scholar 

  4. 4.

    Bouslama-Oueghlani, L., Wehrle, R., Sotelo, C., Dusart, I. (2005) Heterogenity of NG2-expressing cells in the newborn mouse cerebellum. Dev. Biol. 285, 409–421.

    CAS  Article  Google Scholar 

  5. 5.

    Brown, J. P., Couillard-Despres, S., Cooper-Kuhn, C. M., Winkler, J., Aigner, L., Kuhn, H. G. (2003) Transient expression of doublecortin during adult neurogenesis. J. Comp. Neurol. 467, 1–10.

    CAS  Article  Google Scholar 

  6. 6.

    Capes-Davis, A., Tolhurst, O., Dunn, J. M., Jeffrey, P. L. (2005) Expression of doublecortin (DCX) and and doublecortin-like kinase (DCLK) within the developing chick brain. Dev. Dynamics 232, 457–467.

    CAS  Article  Google Scholar 

  7. 7.

    Cooper-Kuhn, C. M., Kuhn, H. G. (2002) Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Brain Res. Dev. Brain Res. 134, 13–21.

    CAS  Article  Google Scholar 

  8. 8.

    Couillard-Despres, S., Winner, B., Schaubeck, S., Aigner, L., Vroemen, M., Weidner, N., Bogdahn, U., Winkler, J., Kuhn, H. G., Aigner, L. (2005) Doublecortin expression levels in adult brain reflect neurogenesis. Eur. J. Neurosci. 21, 1–14.

    Article  Google Scholar 

  9. 9.

    Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B., Vinet, M. C., Friocourt, G. I., McDonnell, N., Reiner, O., Kahn, A., McConnell, S. K., Berwald-Netter, Y., Denoulet, P., Chelly, J. (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23, 247–256.

    CAS  Article  Google Scholar 

  10. 10.

    Gleeson, J. G., Lin, P. T., Flanagan, L. A., Walsh, C. A. (1999) Doublecortin is a microtubule associated protein and is expressed widely by migrating neurons. Neuron 23, 257–271.

    CAS  Article  Google Scholar 

  11. 11.

    Flatten, M. E., Mason, C. A. (1990) Mechanisms of glial-guided neuronal migration in vitro and in vivo. Experientia 46, 907–916.

    Article  Google Scholar 

  12. 12.

    Jin, K., Mao, X. O., Sun, Y., Xie, L., Jin, L., Nishi, E., Klagsbrun, M., Greenberg, D. A. (2002) Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo. J. Neurosci. 22, 5365–5373.

    CAS  Article  Google Scholar 

  13. 13.

    Koizumi, H., Higginbotham, H., Poon, T., Tanaka, T., Brinkman, C. B., Gleeson, J. G. (2006) Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult fore-brain. Nature Neurosci. 9, 779–786.

    CAS  Article  Google Scholar 

  14. 14.

    Komuro, H., Rakic, P. (1998) Distinct modes of neuronal migration in different domains of developing cerebellar cortex. J. Neurosci. 18, 1478–1490.

    CAS  Article  Google Scholar 

  15. 15.

    Komuro, H., Yacubova, E., Yacubova, E., Rakic, P. (2001) Mode and tempo of tangential cell migration in the cerebellar external granular layer. J. Neurosci. 21, 527–540.

    CAS  Article  Google Scholar 

  16. 16.

    Liesi, P. (1992) Neuronal migration on laminin involves nuclear movement inside a preformed process. Exp. Neurol. 117, 103–113.

    CAS  Article  Google Scholar 

  17. 17.

    Liesi, P., Akinshola, E., Matsuba, K., Lange, K., Morest, K. (2003) Cellular migration in the postnatal rat cerebellar cortex: confocal-infrared microscopy and the rapid Golgi method. J. Neurosci. Res. 72, 290–302.

    CAS  Article  Google Scholar 

  18. 18.

    Nacher, J., Alonso-Llosa, G., Rosell, D. R., McEwen, B. S. (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol. Aging 24, 273–284.

    CAS  Article  Google Scholar 

  19. 19.

    Rakic, P. (1981) Neuron-glial interaction during brain development. Trends Neurosci. 4, 184–187.

    Article  Google Scholar 

  20. 20.

    Rakic, P. (1990) Principles of neural cell migration. Experientia 46, 882–891.

    CAS  Article  Google Scholar 

  21. 21.

    Rao, M. S., Shetty, A. K. (2004) Efficacy of doublecortin as a marker to analyze the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur. J. Neurosci. 19, 234–246.

    Article  Google Scholar 

  22. 22.

    Sastry, P. S., Rao, K. S. (2000) Apoptosis and the nervous system. J. Neurochem. 74, 1–20.

    CAS  Article  Google Scholar 

  23. 23.

    Shu, T., Tseng, H.-C, Sapir, T., Stern, P., Zhou, Y., Sanada, K., Fischer, A., Coquelle, F. M., Reiner, O., Tsai, L.-H. (2006) Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M. phase progression. Neuron 49, 25–39.

    CAS  Article  Google Scholar 

  24. 24.

    Takayama, C., Inoue, Y. (2004) Transient expression of GABA(A) receptor alpha2 and alpha3 sub-units in differentiating cerebellar neurons, Brain Res. Dev. Brain Res. 148, 169–177.

    CAS  Article  Google Scholar 

  25. 25.

    Tamura, Y., Kataoka, Y., Cui, Y., Takamori, Y., Watanabe, Y., Yamada, H. (2007) Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo. Eur. J. Neurosci. 25, 3489–3498.

    Article  Google Scholar 

  26. 26.

    Vastagh, Cs., Vig, J., Hamori, J., Takacs, J. (2005) Delayed postnatal settlement of cerebellar Purkinje cells in vermal lobules VI and VII of the mouse. Anat. Embryol. 209, 471–184.

    Article  Google Scholar 

  27. 27.

    Weisheit, G., Gliem, M., Endl, E., Pfeffer, P. L., Busslinger, M., Schilling, K. (2006) Postnatal development of the murine cerebellar cortex: formation and early dispersal of basket, stellate and Golgi neurons. Eur. J. Neurosci. 24, 466–478.

    Article  Google Scholar 

  28. 28.

    Yamanaka, H., Yanagawa, Y., Obata, K. (2004) Development of stellate and basket cells and their apoptosis in mouse cerebellar cortex. Neurosci. Res. 50, 13–22.

    Article  Google Scholar 

  29. 29.

    Yang, H. K., Sundholm-Peters, N. L., Goings, G. E., Walker, A. S., Hyland, K., Szele, F. G. (2004) Distribution of doublecortin expressing cells near the lateral ventricles in the adult mouse brain. J. Neurosci. Res. 76, 282–295.

    CAS  Article  Google Scholar 

  30. 30.

    Zhang, L., Goldman, J. E. (1996) Generation of cerebellar interneurons from dividing progenitors in white matter. Neuron 16, 47–54.

    Article  Google Scholar 

  31. 31.

    Zhang, L., Goldman, J. E. (1996) Developmental fates and migratory pathways of dividing progenitors in the postnatal rat cerebellum. J. Comp. Neurol. 370, 536–550.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. R. Maggi for critical reading of successive versions of the manuscript, and thank for providing Doublecortin (C-18) antibody. This work was supported by OTKA grant T 43478. The Hungarian Science and Technology Foundation together with the Italian Ministry of Foreign Affairs also supported this work in the frame of Hungarian—Italian Intergovernmental Scientific and Technology Cooperation, I-14/03.

Author information

Affiliations

Authors

Corresponding author

Correspondence to J. Takács.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Cite this article

Takács, J., Zaninetti, R., Víg, J. et al. Postnatal Expression of Doublecortin (Dcx) in the Developing Cerebellar Cortex of Mouse. BIOLOGIA FUTURA 59, 147–161 (2008). https://doi.org/10.1556/ABiol.59.2008.2.2

Download citation

Keywords

  • Cerebellum
  • development
  • neuronal migration
  • remodeling