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Identification of tumor differentiation factor (TDF) in select CNS neurons

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Abstract

Identification of central nervous system (CNS) molecules elucidates normal and pathological brain function. Tumor differentiation factor (TDF) is a recently-found protein secreted by the pituitary into the blood. TDF mRNA was detected in brain; not heart, placenta, lung, liver, skeletal muscle, or pancreas. However, TDF has an unclear function. It is not known whether TDF is expressed only by pituitary or by other brain regions. It is also not known precisely where TDF is expressed in the brain or which cells produce TDF. Database searching revealed that this molecule shares no homology with any known protein. Therefore, we investigated the distribution of TDF in the rat brain using immunohistochemistry (IHC) and immunofluorescence (IF). TDF protein was detected in pituitary and most other brain regions. Double-staining for TDF and glial fibrillary acidic protein (GFAP), an astrocyte marker, showed no co-localization. Double-staining for TDF with NeuN, a neuronal marker, showed co-localization. Not all NeuN positive cells were positive for TDF. Western blotting (WB) using NG108 neuroblastoma and GS9L astrocytoma cell lysate revealed TDF immunoreactivity in cultured neuroblastoma, not astrocytoma. These data suggest that TDF is localized in neurons, not in astrocytes. This is the first report of any cellular localization of TDF. TDF may have specific roles as a pituitary-derived hormone and in the CNS, and appears to be produced by distinct CNS neurons, not astroglia.

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Abbreviations

TDF:

Tumor differentiation factor

TDF-R:

TDF receptor

CNS:

Central nervous system

NG108-15:

Neuroblastoma × glioma cell line

GS9L:

Astrocytoma cell line

GFAP:

Glial fibrillary acidic protein

NeuN:

Neuron-specific DNA-binding nuclear protein which functions as a marker for neurons

IHC:

Immunohistochemistry

IF:

Immunofluorescence

WB:

Western blotting

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Acknowledgments

We thank Dr. Kenneth Wallace (Clarkson University) for advice on immunohistochemistry, as well as Dr. Ivan Soltesz (UC Irvine) and Dr. Moses Chao (NYU) for helpful discussions. We also thank Dr. Thomas A. Neubert (Skirball Institute, New York University, New York, NY) and Ms. Jill Pflugheber (ST. Lawrence University, Canton, NY) for providing the NG108 neuroblastoma and GS9L astrocytoma cell lines. This work was supported in part by U.S. Army research office (DURIP grant #W911NF-11-1-0304).

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, 13699-5810, USA

    Alisa G. Woods, Izabela Sokolowska & Costel C. Darie

  2. Centre for Biological Sciences, University of Southampton, Life Sciences Building 85, Southampton, SO17 1BJ, UK

    Katrin Deinhardt

  3. Institute for Life Sciences, University of Southampton, Life Sciences Building 85, Southampton, SO17 1BJ, UK

    Katrin Deinhardt

  4. Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Cristinel Sandu

  5. Neuropsychology Clinic and Psychoeducation Services, SUNY Plattsburgh, Plattsburgh, NY, 12901, USA

    Alisa G. Woods

Authors
  1. Alisa G. Woods
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  2. Izabela Sokolowska
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  3. Katrin Deinhardt
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  4. Cristinel Sandu
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  5. Costel C. Darie
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Corresponding author

Correspondence to Costel C. Darie.

Additional information

A. G. Woods and I. Sokolowska contributed equally to this work.

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Woods, A.G., Sokolowska, I., Deinhardt, K. et al. Identification of tumor differentiation factor (TDF) in select CNS neurons. Brain Struct Funct 219, 1333–1342 (2014). https://doi.org/10.1007/s00429-013-0571-1

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  • DOI: https://doi.org/10.1007/s00429-013-0571-1

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