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Volume 16, Number 9, Issue of May 1, 1996 pp. 2995-3008
Copyright ©1996 Society for NeuroscienceRetrograde Transport of Neurotrophins from the Eye to the Brain in Chick Embryos: Roles of the p75NTR and trkB Receptors
Received Nov. 13, 1995; revised Jan. 19, 1996; accepted Jan. 25, 1996.
Christopher S. von Bartheld1, Reg Williams2, Frances Lefcort3, Douglas O. Clary3, Louis F. Reichardt3, and Mark Bothwell1 1 Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, 2 Department of Developmental Biology, Karolinska Institute, Stockholm, Sweden, and 3 Neuroscience Program, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143
The receptors involved in retrograde transport of neurotrophins from the retina to the isthmo-optic nucleus (ION) of chick embryos were characterized using antibodies to the p75 neurotrophin receptor and trkB receptors. Survival of neurons in the ION has been shown previously to be regulated by target-derived trophic factors with survival promoted or inhibited by ocular injection of brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF), respectively. In the present paper, we show that during the period of target dependence, these neurons express trkB and p75 neurotrophin receptor but not trkA or trkC mRNAs. We also show that BDNF and NT-3 were transported efficiently at low doses, whereas NGF was transported significantly only at higher doses. The transport of BDNF and NT-3 was reduced by high concentrations of NGF or by antibodies to either trkB or the p75 neurotrophin receptor. Thus both receptors help mediate retrograde transport of these neurotrophins. Ocular injection of the comparatively specific trk inhibitor K252a did not reduce transport of exogenous BDNF, but did induce significant neuronal death in the ION, which could not be prevented by co-injection of BDNF. Thus, transport of BDNF alone does not generate a trophic signal at the cell body when axonal trkB is inactivated. In summary, our results indicate that both p75 neurotrophin and trkB receptors can mediate internalization and retrograde transport of BDNF, but activation of trkB seems to be essential for the survival-promoting actions of this neurotrophin.
Key words: BDNF; NT-3; NGF; NGF receptor; development; visual system; eye; retina; trkB; cell death; axonal transport; in situ hybridization; K252a; colchicine
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