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Distinct modulatory actions of TGF-β and LIF on neurotrophin-mediated survival of developing sensory neurons

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Abstract

The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are important for the regulation of survival and differentiation of distinct, largely non-overlapping populations of embryonic sensory neurons. We show here that the multifunctional cytokine transforming growth factor-β (TGF-β) fails to maintain sensory neurons cultured from embryonic day (E) 8 chick dorsal root ganglia (DRG), although DRG neurons are immunoreactive for the TGF-β receptor type II, which is essential for TGF-β signaling. However, in combination with various concentrations of NT-3 and NT-4, but not NGF, TGF-β3 causes a further significant increase in neuron survival. In DRG cell cultures treated with NGF, NT-3, and NT-4, a neutralizing antibody to TGF-β decreases neuron survival suggesting that endogenous TGF-β in these cultures affects the efficacies of neurotrophins. Consistent with this notion and a modulatory role of TGF-β in neurotrophin functions is the observation that TGF-β2 and-β3 immunoreactivities and TGF-β3 mRNA are located in embryonic chick DRG in close association with neurons from E5 onwards. We also show that leukemia inhibitory factor (LIF) significantly decreases NGF-mediated DRG neuron survival. Together, these data indicate that actions and efficacies of neurotrophins are under distinct control by TGF-β and LIF in vitro, and possibly also in vivo.

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  1. Department of Anatomy and Cell Biology, The University of Heidelberg, D-69120, Heidelberg, Germany

    Kerstin Krieglstein & Klaus Unsicker

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  2. Klaus Unsicker
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Special issue dedicated to Dr. Hans Thoenen.

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Krieglstein, K., Unsicker, K. Distinct modulatory actions of TGF-β and LIF on neurotrophin-mediated survival of developing sensory neurons. Neurochem Res 21, 843–850 (1996). https://doi.org/10.1007/BF02532308

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