Target-derived BDNF (brain-derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo-optic nucleus

Neurons in the peripheral nervous system depend on single neurotrophic fact ors, whereas those in the brain are thought to utilize many different troph ic factors. This study examined whether some neurons in the brain criticall y depend on a single trophic factor during development. Neurons in the isth mo-optic nucleus (ION) of chick embryos respond to exogenous brain-derived neurotrophic factor (BDNF). Relatively high concentrations of endogenous BD NF were present in the ION of 14-18-day-old chick embryos. ION target cells in the retina were immunolabeled for BDNF but showed surprisingly low leve ls of BDNF mRNA. These data suggest that ION target cells derive some BDNF from other retinal sources. No BDNF mRNA was detected in the ION itself. IO N neurons had a very efficient retrograde transport system for BDNF and exo genous BDNF arrived in the ION intact. When the ION was deprived of endogen ous trkB ligands by injection of trkB fusion proteins in the eye, cell deat h of ION neurons was enhanced, and this effect was mimicked by BDNF-specifi c blocking antibodies in the eye. TrkB fusion proteins in the retina induce d cell death of ION neurons prior to visible effects on ION target cells in the retina. Immunolabel for endogenous BDNF was sparse in pyknotic ION neu rons, suggesting that ION neurons with low BDNF content were eliminated by apoptosis. These data show that BDNF is an essential target-derived trophic factor for developing ION neurons and thereby validate the neurotrophic hy pothesis for at least one neuronal population in the brain. (C) 2001 Wiley- Liss, Inc.