Reduction of endogenous transforming growth factors β prevents ontogenetic neuron death

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Abstract

We show that following immunoneutralization of endogenous transforming growth factors β (TGF-β) in the chick embryo, ontogenetic neuron death of ciliary, dorsal root and spinal motor neurons was largely prevented, and neuron losses following limb bud ablation were greatly reduced. Likewise, preventing TGF-β signaling by treatment with a TβR-II fusion protein during the period of ontogenetic cell death in the ciliary ganglion rescued all neurons that normally die. TUNEL staining revealed decreased numbers of apoptotic cells following antibody treatment. Exogenous TGF-β rescued the TGF-β-deprived phenotype. We conclude that TGF-β is critical in regulating ontogenetic neuron death as well as cell death following neuronal target deprivation.

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Figure 1: Neutralization of rcTGF-b or TGF-b activity from homgenates by anti-TGF-β or TGF-II-Fc.
Figure 2: Morphology and neuron numbers in chick ciliary ganglia at E10, which is after the main period of ontogenetic ciliary neuron death.
Figure 3: Neuron numbers and apoptosis in ciliary ganglia (CG), dorsal root ganglia (L3; DRG) and the lumbar motoneuron column of embryos treated with anti-TGF-β.
Figure 4: Rescue of the normal phenotype of CG and motoneurons in anti-TGF-β-treated embryos by administration of TGF-β.
Figure 5: Anti-TGF-β rescues lumbar dorsal root ganglia (DRG) and motoneurons (MN) following target deprivation.
Figure 6: TβR-II immunoreactivity in E10 ciliary ganglia following treatment with anti-TGF-β antibodies from E6 to E10.

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Acknowledgements

We thank C.E. Henderson, C. Kalcheim and R. Klein for comments on the manuscript, and U. Hinz, I. Stenull, J. Fey and S.W. Wang for technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft to K.K. and K.U. and by NIH grant NS-20402 to R.W.O.

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Correspondence to Kerstin Krieglstein.

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Krieglstein, K., Richter, S., Farkas, L. et al. Reduction of endogenous transforming growth factors β prevents ontogenetic neuron death. Nat Neurosci 3, 1085–1090 (2000) doi:10.1038/80598

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