Skip to main content

Advertisement

Log in

Expression of Vascular Endothelial Growth Factor Receptor-3 mRNA in the Developing Rat Cerebellum

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Vascular endothelial growth factor receptor (VEGFR)-3, a receptor for VEGF-C and VEGF-D, has recently been suggested to play an important role during neuronal development. To characterize its potential role in CNS ontogenesis, we investigated the spatiotemporal and cellular expression of VEGFR-3 in developing and mature rat cerebellum using in situ hybridization. VEGFR-3 expression appeared as early as E15, and was restricted to the ventricular zone of the cerebellar primordium, the germinative neuroepithelium, but was absent by E20. Instead, the expression area of VEGFR-3 in the cerebellum grew in parallel with cerebellar development. From E20 on, two populations of VEGFR-3-expressing cells can be clearly distinguished in the developing cerebellum: a population of differentiating and postmitotic neurons and the Bergmann glia. VEGFR-3 expression in neurons occurred during the period of neuronal differentiation, and increased with maturation. In particular, the expression of VEGFR-3 mRNA revealed different temporal patterns in different neuronal populations. Neurons generated early, Purkinje cells, and deep nuclear neurons expressed VEGFR-3 mRNA during late embryonic stages, whereas VEGFR-3 transcription in local interneurons appeared by P14 with weaker expression. In addition, Bergmann glia expressed VEGFR-3 throughout cerebellar maturation into adulthood. However, receptor expression was absent in the progenitors in the external granular layer and during further migration. The results of this study suggest that VEGFR-3 has even broader functions than previously thought, regulating both developmental processes and adult neuronal function in the cerebellum.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akimoto J, Itoh H, Miwa T, Ikeda K (1993) Immunohistochemical study of glutamine synthetase expression in early glial development. Brain Res Dev Brain Res 72:9–14

    Article  CAS  PubMed  Google Scholar 

  • Altman J, Bayer SA (1985) Embryonic development of the rat cerebellum. II. Translocation and regional distribution of the deep neurons. J Comp Neurol 231:27–41

    Article  CAS  PubMed  Google Scholar 

  • Altman J, Bayer SA (1987) Development of the precerebellar nuclei in the rat: II. The intramural olivary migratory stream and the neurogenetic organization of the inferior olive. J Comp Neurol 257:490–512

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla A, García-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293

    Article  CAS  PubMed  Google Scholar 

  • Barres BA (1999) A new role for glia: generation of neurons!. Cell 97:667–670

    Article  CAS  PubMed  Google Scholar 

  • Bellamy TC (2006) Interactions between Purkinje neurones and Bergmann glia. Cerebellum 5:116–126

    Article  PubMed  Google Scholar 

  • Brockington A, Lewis C, Wharton S, Shaw PJ (2004) Vascular endothelial growth factor and the nervous system. Neuropathol Appl Neurobiol 30:427–446

    Article  CAS  PubMed  Google Scholar 

  • Campbell K, Götz M (2002) Radial glia: multi-purpose cells for vertebrate brain development. Trends Neurosci 25:235–238

    Article  CAS  PubMed  Google Scholar 

  • Carletti B, Rossi F (2008) Neurogenesis in the cerebellum. Neuroscientist 14:91–100

    Article  PubMed  Google Scholar 

  • Choi JS, Shin YJ, Lee JY, Yun H, Cha JH, Choi JY, Chun MH, Lee MY (2010) Expression of vascular endothelial growth factor receptor-3 mRNA in the rat developing forebrain and retina. J Comp Neurol 518:1064–1081

    Article  CAS  PubMed  Google Scholar 

  • Gubert F, Zaverucha-do-Valle C, Pimentel-Coelho PM, Mendez-Otero R, Santiago MF (2009) Radial glia-like cells persist in the adult rat brain. Brain Res 1258:43–52

    Article  CAS  PubMed  Google Scholar 

  • Hockfield S, McKay RD (1985) Identification of major cell classes in the developing mammalian nervous system. J Neurosci 5:3310–3328

    CAS  PubMed  Google Scholar 

  • Johnson GV, Jope RS (1992) The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration. J Neurosci Res 33:505–512

    Article  CAS  PubMed  Google Scholar 

  • Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K (2004) Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5:74–80

    Article  CAS  PubMed  Google Scholar 

  • Kranich S, Hattermann K, Specht A, Lucius R, Mentlein R (2009) VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cells. Neurochem Int 55:747–753

    Article  CAS  PubMed  Google Scholar 

  • Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S, Tammela T, Haiko P, Karkkainen MJ, Yuan L, Muriel MP, Chatzopoulou E, Bréant C, Zalc B, Carmeliet P, Alitalo K, Eichmann A, Thomas JL (2006) VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci 9:340–348

    Article  PubMed  Google Scholar 

  • Lordkipanidze T, Dunaevsky A (2005) Purkinje cell dendrites grow in alignment with Bergmann glia. Glia 51:229–234

    Article  PubMed  Google Scholar 

  • Matsuda M, Katoh-Semba R, Kitani H, Tomooka Y (1996) A possible role of the nestin protein in the developing central nervous system in rat embryos. Brain Res 723:177–189

    Article  CAS  PubMed  Google Scholar 

  • Millen KJ, Gleeson JG (2008) Cerebellar development and disease. Curr Opin Neurobiol 18:12–19

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Buffo A, Götz M (2005) The novel roles of glial cells revisited: the contribution of radial glia and astrocytes to neurogenesis. Curr Top Dev Biol 69:67–99

    Article  CAS  PubMed  Google Scholar 

  • Raab S, Plate KH (2007) Different networks, common growth factors: shared growth factors and receptors of the vascular and the nervous system. Acta Neuropathol 113:607–626

    Article  CAS  PubMed  Google Scholar 

  • Roy H, Bhardwaj S, Ylä-Herttuala S (2006) Biology of vascular endothelial growth factors. FEBS Lett 580:2879–2887

    Article  CAS  PubMed  Google Scholar 

  • Seki T, Arai Y (1991) The persistent expression of a highly polysialylated NCAM in the dentate gyrus of the adult rat. Neurosci Res 12:503–513

    Article  CAS  PubMed  Google Scholar 

  • Shin YJ, Choi JS, Lee JY, Choi JY, Cha JH, Chun MH, Lee MY (2008) Differential regulation of vascular endothelial growth factor-C and its receptor in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol 116:517–527

    Article  CAS  PubMed  Google Scholar 

  • Shin YJ, Choi JS, Choi JY, Cha JH, Chun MH, Lee MY (2010) Enhanced expression of vascular endothelial growth factor receptor-3 in the subventricular zone of stroke-lesioned rats. Neurosci Lett 469:194–198

    Article  CAS  PubMed  Google Scholar 

  • Sotelo C (2004) Cellular and genetic regulation of the development of the cerebellar system. Prog Neurobiol 72:295–339

    Article  CAS  PubMed  Google Scholar 

  • Supèr H, Del Río, Martínez JA, Pérez-Sust P, Soriano E (2000) Disruption of neuronal migration and radial glia in the developing cerebral cortex following ablation of Cajal-Retzius cells. Cereb Cortex 10:602–613

    Article  PubMed  Google Scholar 

  • Takahashi-Iwanaga H, Kondo H, Yamakuni T, Takahashi Y (1986) An immunohistochemical study on the ontogeny of cells immunoreactive for spot 35 protein, a novel Purkinje cell-specific protein, in the rat cerebellum. Brain Res 394:225–231

    CAS  PubMed  Google Scholar 

  • Tamamaki N, Nakamura K, Okamoto K, Kaneko T (2001) Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex. Neurosci Res 41:51–60

    Article  CAS  PubMed  Google Scholar 

  • Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, Kubo H, Thurston G, McDonald DM, Achen MG, Stacker SA, Alitalo K (2001) Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J 20:1223–1231

    Article  CAS  PubMed  Google Scholar 

  • Yamada K, Watanabe M (2002) Cytodifferentiation of Bergmann glia and its relationship with Purkinje cells. Anat Sci Int 77:94–108

    Article  PubMed  Google Scholar 

  • Yamazaki Y, Morita T (2006) Molecular and functional diversity of vascular endothelial growth factors. Mol Divers 10:515–527

    Article  CAS  PubMed  Google Scholar 

  • Yasuhara T, Shingo T, Kobayashi K, Takeuchi A, Yano A, Muraoka K, Matsui T, Miyoshi Y, Hamada H (2004) Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. Eur J Neurosci 19:1494–1504

    Article  PubMed  Google Scholar 

  • Yuasa S, Kawamura K, Ono K, Yamakuni T, Takahashi Y (1991) Development and migration of Purkinje cells in the mouse cerebellar primordium. Anat Embryol 184:195–212

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The Grant sponsor is from Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs; Grant number: A08-4288-A22023-08N1-00010A.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mun-Yong Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hou, Y., Choi, JS., Shin, YJ. et al. Expression of Vascular Endothelial Growth Factor Receptor-3 mRNA in the Developing Rat Cerebellum. Cell Mol Neurobiol 31, 7–16 (2011). https://doi.org/10.1007/s10571-010-9530-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-010-9530-z

Keywords

Navigation