Advertisement

Acta Biologica Hungarica

, Volume 59, Issue 2, pp 147–161 | Cite as

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

  • J. TakácsEmail author
  • Roberta Zaninetti
  • Julianna Víg
  • Cs. Vastagh
  • J. Hámori
Article
First Online:

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.

Keywords

Cerebellum development neuronal migration remodeling 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

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.

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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  16. 16.
    Liesi, P. (1992) Neuronal migration on laminin involves nuclear movement inside a preformed process. Exp. Neurol. 117, 103–113.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  19. 19.
    Rakic, P. (1981) Neuron-glial interaction during brain development. Trends Neurosci. 4, 184–187.CrossRefGoogle Scholar
  20. 20.
    Rakic, P. (1990) Principles of neural cell migration. Experientia 46, 882–891.CrossRefGoogle 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.CrossRefGoogle Scholar
  22. 22.
    Sastry, P. S., Rao, K. S. (2000) Apoptosis and the nervous system. J. Neurochem. 74, 1–20.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  30. 30.
    Zhang, L., Goldman, J. E. (1996) Generation of cerebellar interneurons from dividing progenitors in white matter. Neuron 16, 47–54.CrossRefGoogle 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.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest 2008

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.

Authors and Affiliations

  • J. Takács
    • 1
    Email author
  • Roberta Zaninetti
    • 2
  • Julianna Víg
    • 1
  • Cs. Vastagh
    • 3
  • J. Hámori
    • 1
  1. 1.Infobionic and Neurobiological Plasticity Research Group of the Hungarian Academy of SciencesPéter Pázmány Catholic University - Semmelweis UniversityBudapestHungary
  2. 2.Laboratory of Developmental Neuroendocrinology, Department of Endocrinology, Centre of Excellence on Neurodegenerative DiseasesUniversity of MilanoMilanoItaly
  3. 3.Institute of Experimental MedicineHungarian Academy of SciencesBudapestHungary

Personalised recommendations

Cite article

Buy options