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Expression patterns of erythropoietin and its receptor in the developing midbrain

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Abstract

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.

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Abbreviations

BLBP :

Brain lipid-binding protein

EPO :

Erythropoietin

EPOR :

EPO receptor

GLAST :

Astrocyte-specific glutamate transporter

HIF-1 :

Hypoxia-inducible factor 1

TBS :

Tris-buffered saline

TBST :

TBS/Tween

TMN :

Trigeminal mesencephalic nucleus

TUNEL :

Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling

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Acknowledgments

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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Authors and Affiliations

  1. Department of Anatomy and Embryology, Georg-August University, 37075 , Göttingen, Germany

    W. Knabe, S. Washausen & H. J. Kuhn

  2. Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, 37075 , Göttingen, Germany

    F. Knerlich, A. L. Sirén & H. Ehrenreich

  3. Department of Biochemistry and Molecular Cell Biology, Georg-August University, 37075 , Göttingen, Germany

    T. Kietzmann

  4. Department of Informatics, Technical University, 09107 , Chemnitz, Germany

    G. Brunnett

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  1. W. Knabe
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  2. F. Knerlich
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Correspondence to H. Ehrenreich.

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W. Knabe and F. Knerlich contributed equally to this work

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Knabe, W., Knerlich, F., Washausen, S. et al. Expression patterns of erythropoietin and its receptor in the developing midbrain. Anat Embryol 207, 503–512 (2004). https://doi.org/10.1007/s00429-003-0365-y

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