Anatomy and Embryology

, Volume 207, Issue 6, pp 503–512 | Cite as

Expression patterns of erythropoietin and its receptor in the developing midbrain

  • W. Knabe
  • F. Knerlich
  • S. Washausen
  • T. Kietzmann
  • A. L. Sirén
  • G. Brunnett
  • H. J. Kuhn
  • H. Ehrenreich
Original Article


The expression patterns of erythropoietin (EPO) and its receptor (EPOR) were investigated in the midbrain and in adjacent parts of the synencephalon and hindbrain of embryonic C57Bl mice. On embryonic (E) day 8 (E8), virtually all neuroepithelial cells expressed EPOR. After neural tube closure, subsets of these cells downregulated EPOR. In contrast, radial glial cells were EPOR-immunolabeled from E11 onwards. Simultaneously, subpopulations of early developing neurons upregulated EPO and expressed HIF-1, known to transcriptionally activate EPO. Three-dimensional reconstructions revealed subpopulations of EPO-expressing neurons: (1) in the trigeminal mesencephalic nucleus (TMN), (2) at the rostral transition of the midbrain and synencephalon, (3) in the basal plate of the midbrain, (4) in the trigeminal motor nucleus, and (5) in the trigeminal principal sensory nucleus. In the rostral midbrain and synencephalon, EPO-immunoreactive neurons were attached to EPOR-expressing radial glial cells. The identity of radial glial cells was proven by their immunoreactivity for antibodies against astrocyte-specific glutamate transporter, brain lipid-binding protein, and nestin. From E12.5 onwards EPOR was downregulated in radial glial cells. Viable neurons of the TMN continued to express EPO and upregulated EPOR. Our findings provide new evidence that components of the EPO system are present in distinct locations of the embryonic brain and, by interactions between neurons and radial glial cells as well as among clustered TMN neurons, may contribute to its morphogenesis. Whether the observed expression patterns of EPO and EPOR may reflect EPO-mediated trophic and/or antiapoptotic effects on neurons is discussed.


Apoptosis Erythropoietin Midbrain Mouse embryos Radial glial cells 



Brain lipid-binding protein




EPO receptor


Astrocyte-specific glutamate transporter


Hypoxia-inducible factor 1


Tris-buffered saline




Trigeminal mesencephalic nucleus


Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling



This work was supported by the Deutsche Forschungsgemeinschaft (KN 525/1-1, KN 525/1-2 to W. K. and H.-J. K., BR 1185/4-1 to G. B., Sonderforschungsbereich 402-A1 and Graduiertenkolleg 335 to T. K.), and by the Max Planck Society (H. E.).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • W. Knabe
    • 1
  • F. Knerlich
    • 2
  • S. Washausen
    • 1
  • T. Kietzmann
    • 3
  • A. L. Sirén
    • 2
  • G. Brunnett
    • 4
  • H. J. Kuhn
    • 1
  • H. Ehrenreich
    • 2
  1. 1.Department of Anatomy and EmbryologyGeorg-August UniversityGöttingenGermany
  2. 2.Max Planck Institute for Experimental MedicineGöttingenGermany
  3. 3.Department of Biochemistry and Molecular Cell BiologyGeorg-August UniversityGöttingenGermany
  4. 4.Department of InformaticsTechnical UniversityChemnitzGermany

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