Hostname: page-component-848d4c4894-m9kch Total loading time: 0 Render date: 2024-05-14T14:48:37.029Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunohistochemical analysis of the neurotrophins BDNF and NT-3 and their receptors trk B, trk C, and p75 in the developing chick retina

Published online by Cambridge University Press:  02 June 2009

Indranil Das ,
Barbara L. Hempstead ,
Peter R. Macleish  and
Janet R. Sparrow
Indranil Das
Affiliation:
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Cornell University Medical College, New York Division of Hematology and Oncology, Department of Medicine, Cornell University Medical College, New York
Barbara L. Hempstead
Affiliation:
Division of Hematology and Oncology, Department of Medicine, Cornell University Medical College, New York
Peter R. Macleish
Affiliation:
Neuroscience Institute, Morehouse School of Medicine, Atlanta
Janet R. Sparrow
Affiliation:
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Cornell University Medical College, New York
Get access Rights & Permissions [Opens in a new window]

Abstract

The neurotrophins are trophic and mitogenic factors critical for the development of specific classes of neurons in the central and peripheral nervous systems. In the retina, BDNF and NT-3 have been shown to promote the survival of differentiated ganglion cells (Rodriguez-Tebar et al., 1989; De La Rosa et al., 1994). NT-3 has also been demonstrated to support the survival of amacrine cells and facilitates the differentiation of retinal neurons in culture (De La Rosa et al., 1994). Here, we examine immunohistochemically the expression of BDNF and NT-3 proteins, their cognate receptors, trk B and trk C, respectively, and the p75 neurotrophin receptor in the developing chick retina. At E8, the earliest stage of retinal development examined, all of these proteins exhibit diffuse expression throughout the width of the retina, with the strongest reactivity in the innermost layers. A gradual restriction in expression to ganglion cells and amacrine cells, the staining of which is most prominent at E15, is followed by a downregulation of expression with the strongest immunoreactivity persisting in the ganglion cell layer. Overlapping patterns of expression throughout embryonic development indicate a colocalization of the neurotrophins and their receptors, although NT-3 and p75 alone are present in the inner plexiform layer and only p75 is observed in the outer plexiform layer. Although some of the immunoreactivity for BDNF, NT-3, and their receptors in retina may reflect trophic mechanisms operating in association with the optic tectum and isthmo-optic nucleus, the colocalization of ligands and receptors in retina strengthens the assertion that these neurotrophins function locally during development.

Keywords

RetinaNeurotrophinstrksp75Chick
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 5 , September 1997 , pp. 835 - 842
Copyright
Copyright © Cambridge University Press 1997

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adler, R. & Hatlee, M. (1989). Plasticity and differentiation of embryonic retinal cells after terminal mitosis. Science 243, 391–393.CrossRefGoogle ScholarPubMed
Altshuler, D. & Cepko, C. (1992). A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro. Development 114, 947–957.CrossRefGoogle ScholarPubMed
Altshuler, D., Lo Turco, J.J., Rush, J. & Cepko, C. (1993). Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development 119, 1317–1328.CrossRefGoogle ScholarPubMed
Anchan, R.M., Reh, T.A., Angello, J., Balliet, A. & Walker, M. (1991). EGF and TGF-alpha stimulate retinal neuroepithelial cell proliferation in vitro. Neuron 6, 923–936.CrossRefGoogle ScholarPubMed
Austin, C.P., Feldman, D.E., Ida, J.A. & Cepko, C.L. (1995). Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch. Development 121, 3637–3650.CrossRefGoogle ScholarPubMed
Barker, P.A. & Shooter, E.M. (1994). Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC 12 cells. Neuron 13, 203–215.CrossRefGoogle Scholar
Berkemeier, L.R., Winslow, J.W., Kaplan, D.R., Nikolics, K., Goeddel, D.V. & Rosenthal, A. (1991). Neurotropin-5: A novel neurotrophic factor that activates trk and trkB. Neuron 7, 857–866.CrossRefGoogle ScholarPubMed
Bindra, P.S., Knowles, R. & Buckley, K.M. (1993). Conservation of the amino acid sequence of SV2, a transmembrane transporter in synaptic vesicles and endocrine cells. Gene 137, 299–302.CrossRefGoogle ScholarPubMed
Both well, M. (1995). Functional interactions of neurotrophins and neurotrophin receptors. Annual Review of Neuroscience 18, 223–253.CrossRefGoogle Scholar
Bovolenta, P., Frade, J.-M, Marti, E., Rodriguez-Pena, M.-A., Barde, Y.-A. & Rodriguez-Tebar, A. (1996). Neurotrophin-3 antibodies disrupt the normal development of the chick retina. Journal of Neuroscience 16, 4402–4410.CrossRefGoogle ScholarPubMed
Buckley, K. & Kelly, R.B. (1985). Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells. Journal of Cell Biology 100, 1284–1294.CrossRefGoogle ScholarPubMed
Carmignoto, G., Comelli, M.C., Candeo, P., cavicchioli, L., Yan, Q., Merighi, A. & Maffei, L. (1991). Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina. Experimental Neurology 111, 302–311.CrossRefGoogle ScholarPubMed
Chao, M.V. (1992). Neurotrophin receptors: A window into neuronal differentiation. Neuron 9, 583–593.CrossRefGoogle ScholarPubMed
Chittka, A. & Chao, M.V. (1995). p75 neurotrophin receptor. Neural Notes (Promega) 1, 9–11.Google Scholar
Cohen-Cory, S. & Fraser, S.E. (1994). BDNF in the development of the visual sysem of Xenopus. Neuron 12, 747–761.CrossRefGoogle Scholar
Cohen-Cory, S. & Fraser, S.E. (1995). Effects of brain-derived neurotrophic factor on optic axon branching and remodeling in vivo. Nature 378, 192–196.CrossRefGoogle ScholarPubMed
Coulombre, A.J. (1955). Correlations of structural and biochemical changes in the developing retina of the chick. American Journal of Anatomy 96, 153–189.CrossRefGoogle ScholarPubMed
Davies, A.M. (1994). The role of neurotrophins in the developing nervous system. Journal of Neurobiology 25, 1134–1348.CrossRefGoogle ScholarPubMed
De La Rosa, E.J., Arribas, A., Frade, J.M. & Rodriguez-Tebar, A. (1994). Role of neurotrophins in the control of neural development: Neurotrophin-3 promotes both neuron differentiation and survival of cultured chick retinal cells. Neuroscience 58, 347–352.CrossRefGoogle ScholarPubMed
Dechant, G., Biffo, S., Okazawa, H., Kolbeck, R., Pottgiesser, J. & Barde, Y.A. (1993). Expression and binding characteristics of the BDNF receptor chick trkB. Development 119, 545–558.CrossRefGoogle ScholarPubMed
Donovan, M.J., Miranda, R.C., Kraemer, R., McCaffrey, T.A., Tessa-rollo, L., Mahadeo, D., Sharif, S., Kaplan, D.R., Tsoulfas, P., Parada, L., Dominique Toran-Allerand, C, Hajjar, D.P. & Hempstead, B.L. (1995). Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. American Journal of Pathology 147, 309–324.Google ScholarPubMed
Dowling, J.E. (1987). The Retina: An Approachable Part of the Brain. Cambridge: Belknap Press of Harvard University Press.Google Scholar
Drager, U.C., Edwards, D.L. & Barnstable, C.J. (1984). Antibodies against filamentous components in discrete cell types of the mouse retina. Journal of Neuroscience 4, 2025–2042.CrossRefGoogle ScholarPubMed
Ernfors, P., Merlio, J.-P. & Persson, H. (1992). Cells expressing mRNA for neurotrophins and their receptors during embryonic rat development. European Journal of Neuroscience 4, 1140–1158.CrossRefGoogle ScholarPubMed
Escandon, E., Soppet, D., Rosenthal, A., Mendoza-Ramirez, J.-L., Szonyi, E., Burton, L.E., Henderson, C.E., Parada, L.F. & Nikolics, K. (1994). Regulation of neurotrophin receptor expression during embryonic and postnatal development. Journal of Neuroscience 14, 2054–2068.CrossRefGoogle ScholarPubMed
Fekete, D.M., Perez-Miguelsanz, J., Ryder, E.F. & Cepko, C.L. (1994). Clonal analysis in the chicken retina reveals tangential dispersion of clonally related cells. Developmental Biology 166, 666–682.CrossRefGoogle ScholarPubMed
Frade, J.M., Rodriguez-Tebar, A. & Barde, Y.-A. (1996). Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383, 166–168.CrossRefGoogle ScholarPubMed
Fritzsch, B., Crapon de Caprona, M.-D. & Clarke, P.G.H. (1990). Development of two morphological types of retinopetal fibers in chick embryos, as shown by the diffusion along axons of a carbocyanine dye in the fixed retina. Journal of Comparative Neurology 300, 405–421.CrossRefGoogle ScholarPubMed
Garner, A.S. & Large, T.H. (1994). Isoforms of the avian trkC receptor: A novel kinase insertion disassociates transformation and process outgrowth from survival. Neuron 13, 457–472.CrossRefGoogle Scholar
Garner, A.S., Menegay, H.J., Boeshore, K.L., Xie, X.-Y, Voci, J.M., Johnson, J.E. & Large, T.H. (1996). Expression of trkB receptor isoforms in the developing avian visual system. Journal of Neuroscience 16, 1740–1752.CrossRefGoogle ScholarPubMed
Guillemot, F & Cepko, C.L. (1992). Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development. Development 114, 743–754.CrossRefGoogle Scholar
Hallbook, F., Backstrom, A., Kullander, K., Ebendal, T. & Carri, N.G. (1996). Expression of neurotrophins and trks receptors in the avian retina. Journal of Comparative Neurology 364, 664–676.3.0.CO;2-1>CrossRefGoogle Scholar
Harris, W.A. & Messersmith, S.L. (1992). Two cellular inductions involved in photoreceptor determination in the Xenopus retina. Neuron 9, 357–372.CrossRefGoogle ScholarPubMed
Hempstead, B.L., Martin-Zanca, D., Kaplan, D.R., Parada, L.F. & Chao, M.V. (1991). High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350, 678–683.CrossRefGoogle ScholarPubMed
Herzog, K.H., Bailey, K. & Barde, Y.A. (1994). Expression of the BDNF gene in the developing visual system of the chick. Development 120, 1643–1649.CrossRefGoogle ScholarPubMed
Heuer, J.G., Fatemie-Nainie, S., Wheeler, E.F. & Bothwell, M. (1990). Structure and developmental expression of the chicken NGF receptor. Developmental Biology 137, 287–304.CrossRefGoogle ScholarPubMed
Hicks, D. & Courtois, Y. (1992). Fibroblast growth factor stimulates photoreceptor differentiation in vitro. Journal of Neuroscience 12, 2022–2033.CrossRefGoogle ScholarPubMed
Huber, L.J., Hempstead, B. & Donovan, M.J. (1996). Neurotrophin and neurotrophin receptors in human fetal kidney. Developmental Biology 179, 369–381.CrossRefGoogle ScholarPubMed
Hughes, W.F. & McLoon, S.C. (1979). Ganglion cell death during normal retinal development in the chick: Comparison with cell death induced by early target field destruction. Experimental Neurology 66, 587–601.CrossRefGoogle ScholarPubMed
Hunter, D.D., Murphy, M.D., Olsson, C.V. & Brunken, W.J. (1992). S-laminin expression in adult and developing retinae: A potential cue for photoreceptor morphogenesis. Neuron 8, 399–413.CrossRefGoogle ScholarPubMed
Johnson, J.E., Barde, Y.-A., Schwab, M. & Thoenen, H. (1986). Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. Journal of Neuroscience 6, 3031–3038.CrossRefGoogle ScholarPubMed
Kaplan, D.R., Hempstead, B.L., Martin-Zanca, D., Chao, M.V. & PaRada, L.F. (1991). The trk proto-oncogene product: A signal transducing receptor for nerve growth factor. Science 252, 554–558.CrossRefGoogle ScholarPubMed
Kelley, M.W., Turner, J.K. & Reh, T.A. (1994). Retinoic acid promotes differentiation of photoreceptors in vitro. Development 120, 2091–2102.CrossRefGoogle ScholarPubMed
Klein, R., Nanduri, V., Jing, S., Lamballe, F., Tapley, P., Bryant, S., Cordon-Cardo, C, Jones, K.R., Reichardt, L.F. & Barbacid, M. (1991). The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotropin-3. Cell 66, 395–403.CrossRefGoogle Scholar
Knight, J.K. & Raymond, PA. (1990). Time course of opsin expression in developing rod photoreceptors. Development 110, 1115–1120.CrossRefGoogle ScholarPubMed
Kokaia, Z., Bengzon, J., Metsis, M., Kokaia, M., Persson, H. & Lindvall, O. (1993). Coexpression of neurotrophins and their receptors in neurons of the central nervous system. Proceedings of the National Academy of Sciences of the U.S.A. 90, 6711–6715.CrossRefGoogle ScholarPubMed
Lamballe, F., Klein, R. & Barbacid, M. (1991). TrkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell 66, 967–979.CrossRefGoogle ScholarPubMed
Leibrock, J., Lottspeich, F, Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H. & Barde, Y.A. (1989). Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341, 149–152.CrossRefGoogle ScholarPubMed
Lillien, L. (1994). Neurogenesis in the vertebrate retina. Perspectives in Developmental Neurobiology 2, 175–182.Google ScholarPubMed
Lillien, L. (1995). Changes in retinal cell fate induced by overexpression of EGF receptor. Nature 377, 158–162.CrossRefGoogle ScholarPubMed
Lillien, L. & Cepko, C. (1992). Control of proliferation in the retina: Temporal changes in responsiveness to FGF and TGF alpha. Development 115, 253–266.CrossRefGoogle ScholarPubMed
Maisonpierre, P.C., Belluscio, L., Conover, J.C. & Yancopoulos, G.D. (1992). Gene sequences of chicken BDNF and NT-3. DNA Sequence 3, 49–54.CrossRefGoogle ScholarPubMed
Maisonpierre, P.C., Belluscio, L., Friedman, B., Alderson, R.F., Wiegand, S.J., Furth, M.E., Lindsay, R.M. & Yancopoulos, G.D. (1990). NT-3, BDNF, and NGF in the developing rat nervous system: Parallel as well as reciprocal patterns of expression. Neuron 5, 501–509.CrossRefGoogle ScholarPubMed
Mansour-Robaey, S., Clarke, D.B., Wang, Y.C, Bray, G.M. & Aguayo, A.J. (1994). Effects of ocular injury and the administration of brain-derived neurotrophic factor (BDNF) on the survival and regrowth of axotomized retinal ganglion cells. Proceedings in the National Academy of Sciences of the U.S.A. 91, 1632–1636.CrossRefGoogle ScholarPubMed
Martinez-Morales, J.-R., Marti, E., Frade, J.M. & Rodriguez-Tebar, A. (1995). Developmentally regulated vitronectin influences cell differentiation, neuron survival and process outgrowth in the developing chicken retina. Neuroscience 68, 245–253.CrossRefGoogle ScholarPubMed
Mascarelli, F., Raulais, D., Counis, M.F. & Courtois, Y. (1987). Characterization of acidic and basic fibroblast growth factors in brain, retina, and vitreous chick embryo. Biochemical and Biophysical Research Communications 146, 478–486.CrossRefGoogle ScholarPubMed
Matter, J.M., Matter-Sadzinski, L. & Ballivet, M. (1995). Activity of the beta 3 nicotinic receptor promoter is a marker of neuron fate determination during retina development. Journal of Neuroscience 15, 5919–5928.CrossRefGoogle ScholarPubMed
Mendell, L.M. (1994). Neurotrophic factors and the specification of neural function. Neuroscientist 21–29.Google Scholar
Middlemas, D.S., Lindberg, R.A. & Hunter, T. (1991). trkB, a neural receptor protein-tyrosine kinase: Evidence for a full-length and two truncated receptors. Molecular and Cellular Biology 11, 143–153.Google ScholarPubMed
Miranda, R.C., Sohrabji, F. & Dominique Toran-Allerand, C. (1993). Neuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions. Proceedings of the National Academy of Sciences of the U.S.A. 90, 6439–6443.CrossRefGoogle ScholarPubMed
Prada, C., Puga, J., Perez-Mendez, L., Lopez, R. & Ramirez, G. (1991). Spatial and temporal patterns of neurogenesis in the chick retina. European Journal of Neuroscience 3, 559–569.CrossRefGoogle ScholarPubMed
Reh, T.A. & Tully, T. (1986). Regulation of tyrosine hydroxylase-containing amacrine cell number inlarval frog retina. Developmental Biology 114, 463–469.CrossRefGoogle ScholarPubMed
Rickman, D.W. & Brecha, N.C. (1995). Expression of the proto-oncogene, trk, receptors in the developing rat retina. Visual Neuroscience 12, 215–222.CrossRefGoogle ScholarPubMed
Rodriguez-Tebar, A., Jeffrey, PL., Thoenen, H. & Barde, Y.-A. (1989). The survival of chick retinal ganglion cells in response to brain derived neurotrophic factor depends on their embryonic age. Developmental Biology 136, 296–303.CrossRefGoogle ScholarPubMed
Schecterson, L.C. & Bothwell, M. (1992). Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons. Neuron 9, 449–463.CrossRefGoogle ScholarPubMed
Snow, R.L. & Robson, J.A. (1994). Ganglion cell neurogenesis, migration and early differentiation in the chick retina. Neuroscience 58, 399–409.CrossRefGoogle ScholarPubMed
Soppet, D., Escandon, E., Maragos, J., Middlemas, D.S., Reid, S.W., Blair, J., Burton, L.E., Stanton, B.R., Kaplan, D.R., Hunter, T, Nikolics, K. & Parada, L.F. (1991). The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell 65, 895–903.CrossRefGoogle ScholarPubMed
Sparrow, J.R., Hicks, D. & Barnstable, C.J. (1990). Cell commitment and differentiation in explants of embryonic rat neural retina. Comparison with the developmental potential of dissociated retina. Developmental Brain Research 51, 69–84.CrossRefGoogle ScholarPubMed
Thanos, S., Bark, M., Barde, Y.-A. & Vanselow, J. (1989). Survival and elongation of adult rat retinal ganglion cells. European Journal of Neuroscience 1, 19–26.CrossRefGoogle ScholarPubMed
Thoenen, H. (1995). Neurotrophins and neuronal plasticity. Science 270, 593–597.CrossRefGoogle ScholarPubMed
Tsoulfas, P., Soppet, D., Escandon, E., Tessarollo, L., Mendoza-Ramirez, J.L., Nikolics, K. & Parada, L.F. (1993). The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC 12 cells. Neuron 10, 975–990.CrossRefGoogle Scholar
von Bartheld, C.S., Williams, R., Lefcort, F., Clary, D.O., Reichardt, L.F. & Bothwell, M. (1996 a). Retrograde transport of neurotrophins from the eye to the brain in chick embryos: Roles of the p75NTR and trkB receptors. Journal of Neuroscience 16, 2995–3008.CrossRefGoogle Scholar
von Bartheld, C.S., Byers, M.R., Williams, R. & Bothwell, M. (1996 b). Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system. Nature 379, 830–833.CrossRefGoogle ScholarPubMed
von Bartheld, C.S., Heuer, J.G. & Bothwell, M. (1991). Expression of nerve growth factor (NGF) receptors in the brain and retina of chick embryos: Comparison with cholinergic development. Journal of Comparative Neurology 310, 103–129.CrossRefGoogle ScholarPubMed
von Bartheld, C.S., Kinoshita, Y, Prevette, D., Yin, Q.-W., Oppen-heim, R.W. & Bothwell, M. (1994). Positive and negative effects of neurotrophins on the isthmo-optic nucleus in chick embryos. Neuron 12, 639–654.CrossRefGoogle ScholarPubMed
Waid, D.K. & McLoon, S.C. (1995). Immediate differentiation of ganglion cells following mitosis in the developing retina. Neuron 14, 117–124.CrossRefGoogle ScholarPubMed
Wanaka, A., Milbrandt, J. & Johnson, E.M.J. (1991). Expression of FGF receptor gene in rat development. Development 111, 455–468.CrossRefGoogle ScholarPubMed
Watanabe, T. & Raff, M.C. (1990). Rod photoreceptor development in vitro: Intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina. Neuron 2, 461–467.CrossRefGoogle Scholar
Watanabe, T. & Raff, M.C. (1992). Diffusible rod-promoting signals in the developing rat retina. Development 114, 899–906.CrossRefGoogle ScholarPubMed
Wilkinson, D.G., Bhatt, S. & McMahon, A.P. (1989). Expression pattern of the FGF-related proto-oncogene int-2 suggests multiple roles in fetal development. Development 105, 131–136.CrossRefGoogle ScholarPubMed
Williams, R.W. & Goldowitz, D. (1992). Lineage versus environment in embryonic retina: A revisionist perspective. Trends in Neurosciences 15, 368–373.CrossRefGoogle ScholarPubMed
Wright, E.M., Vogel, K.S. & Davies, A.M. (1992). Neurotrophic factors promote the maturation of developing sensory neurons before they become dependent on these factors for survival. Neuron 9, 139–150.CrossRefGoogle ScholarPubMed
Zipursky, S.L. & Rubin, G.M. (1994). Determination of neuronal cell fate: Lessons from the R7 neuron of Drosophila. Annual Review of Neuroscience 17, 373–397.CrossRefGoogle ScholarPubMed