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Published October 10, 1996 | public
Journal Article

The Cellular Patterns of BDNF and trkB Expression Suggest Multiple Roles for BDNF during Xenopus Visual System Development

Abstract

The temporal patterns of BDNF andtrkBexpression in the developingXenopus laevistadpole, and the responsiveness of retinal ganglion cells to BDNF, both in culture andin vivo,suggest significant roles for this neurotrophin during visual system development (Cohen-Cory and Fraser,Neuron12, 747–761, 1994;Nature378, 192–196, 1995). To examine the potential roles of this neurotrophin within the developing retina and in its target tissue, the optic tectum, we studied the cellular sites of BDNF expression byin situhybridization. In the developing optic tectum, discrete groups of cells juxtaposed to the tectal neuropil where retinal axons arborize expressed BDNF, supporting the target-derived role commonly proposed for this neurotrophin. In the retina, retinal ganglion cells, ciliary margin cells, and a subset of cells in the inner nuclear layer expressed the BDNF gene. The expression of BDNF coincided with specifictrkBexpression by both retinal ganglion cells and amacrine cells, as well as with the localization of functional BDNF binding sites within the developing retina, as shown byin situhybridization and BDNF cross-linking studies. To test for a possible role of endogenous retinal BDNF during development, we studied the effects of neutralizing antibodies to BDNF on the survival of retinal ganglion cells in culture. Exogenously administered BDNF increased survival, whereas neutralizing antibodies to BDNF significantly reduced baseline retinal ganglion cell survival and differentiation. This suggests the presence of an endogenous retinal source of neurotrophic support and that this is most likely BDNF itself. The retinal cellular patterns of BDNF andtrkBexpression as well as the effects of neutralizing antibodies to this neurotrophin suggest that, in addition to a target-derived role, BDNF plays both autocrine and/or paracrine roles during visual system development.

Additional Information

© 1996 Academic Press, Inc. Received for publication March 22, 1996. Accepted June 26, 1996. We are grateful to Dr. J. Carnahan of Amgen. Inc., for providing the BDNF antibodies, to Genentech, Inc., for providing recombinant BDNF, and to Dr. P. Isackson for providing the Xenopus BDNF cDNA clone used in this study. We also thank K. Woo, D. DeSha. Drs. S. Elkabes. and J. Shih for comments to the manuscript and D. Akutagawa, A. Poon. and J. L. Mendoza-Ramírez for assistance with technical aspects of this work. This work was supported by the Helen Hay Whitney Foundation and NIMH Silvio Conte Center Grant MH49l76.

Additional details

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August 19, 2023
Modified:
October 18, 2023