Functions of Growth/Differentiation Factor-15 (GDF-15) in Neuron Survival and peripheral Myelination
Final Report Abstract
GDF-15 is a relatively novel member of the TGF-ß superfamily discovered in our laboratory. Our initial studies revealed a wide distribution in the CNS and PNS, and potential as a neurotrophic factor. We generated a knockout, which shows progressive postnatal motor and sensory (DRG) neuron loss, which equally affects all trk and c-ret subpopulations. We found GDF-15 expressed in human glioma and glioblastoma cells lines, without consistently affecting proliferation and invasiveness in vitro. Further studies revealed implications of GDF-15 in embryonic and postnatal neurogenesis in the ganglionic eminence and hippocampus. With regard to peripheral myelination we found GDF-15 to be synthesized and released by Schwann cells and conducted a detailed analysis of the knockout hypermyelination phenotype. Preliminary results suggest that CXCR4 might function as a (co-)receptor for GDF-15.
Publications
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(2008). Expression and putative functions of GDF-15, a member of the TGF-ß superfamily, in human glioma and glioblastoma cell lines. Cancer Letters 270: 30-39
Strelau, J., Schmeer, C., Peterziel, H., Paech, T., Herold-Mende, C., Steiner, H., Weller, M., Unsicker, K.
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(2009). Progressive postnatal motoneuron loss in mice lacking GDF-15. J. Neuroscience 29: 13640-13648
Strelau, J., Strzelczyk, A.P., Rusu, P., Bendner, G., Wiese, S., Diella, F., Altick, A.L., von Bartheld, C.S., Klein, R., Sendtner, M., Unsicker, K.
