THE CELLULAR-PATTERNS OF BDNF AND TUKB EXPRESSION SUGGEST MULTIPLE ROLES FOR BDNF DURING XENOPUS VISUAL-SYSTEM DEVELOPMENT

The temporal patterns of BDNF and trkB expression in the developing Xe nopus laevis tadpole, and the responsiveness of retinal ganglion cells to BDNF, both in culture and in vivo, suggest significant roles for t his neurotrophin during visual system development (Cohen-Cory and Fras er, Neuron 12, 747-761, 1994; Nature 378, 192-196, 1995). To examine t he potential roles of this neurotrophin within the developing retina a nd in its target tissue, the optic tectum, we studied the cellular sit es of BDNF expression by in situ hybridization. In the developing opti c tectum, discrete groups of cells juxtaposed to the tectal neuropil w here retinal axons arborize expressed BDNF, supporting the target-deri ved role commonly proposed for this neurotrophin. In the retina, retin al ganglion cells, ciliary margin cells, and a subset of cells in the inner nuclear layer expressed the BDNF gene. The expression of BDNF co incided with specific trkB expression by both retinal ganglion cells a nd amacrine cells, as well as with the localization of functional BDNF binding sites within the developing retina, as shown by in situ hybri dization and BDNF cross-linking studies. To test for a possible role o f endogenous retinal BDNF during development, we studied the effects o f neutralizing antibodies to BDNF on the survival of retinal ganglion cells in culture. Exogenously administered BDNF increased survival, wh ereas neutralizing antibodies to BDNF significantly reduced baseline r etinal ganglion cell survival and differentiation. This suggests the p resence of an endogenous retinal source of neurotrophic support and th at this is most likely BDNF itself. The retinal cellular patterns of B DNF and trkB expression as well as the effects of neutralizing antibod ies to this neurotrophin suggest that, in addition to a target-derived role, BDNF plays both autocrine and/or paracrine roles during visual system development. (C) 1996 Academic Press, Inc.