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Expression of the proto-oncogene, trk, receptors in the developing rat retina

Published online by Cambridge University Press:  02 June 2009

Dennis W. Rickman
Affiliation:
Department of Ophthalmology, St. Louis University and Anheuser-Busch Eye Institute, St. Louis
Nicholas C. Brecha
Affiliation:
Department of Anatomy and Cell Biology, Department of Medicine, Brain Research Institute, Jules Stein Eye Institute and the CURE Gastroenteric Biology Center, UCLA School of Medicine, Los Angeles

Abstract

The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 are important in a variety of developmental processes in the peripheral and central nervous systems. These molecules bind to a low-affinity receptor and to distinct high-affinity receptors. The high-affinity receptor for NGF is the proto-oncogene product, p140trkA(trkA). Isoforms of p140trkA, p145trkB(trkB), and p140trkC(trkC), are the primary high-affinity receptors for BDNF and NT-3, respectively. We evaluated the developmental regulation of the high-affinity neurotrophin receptors in the rat retina using polyclonal antibodies directed to a highly conserved region of the C-terminus of the p140trkA isoforms (pantrk) and antibodies directed to unique amino-acid sequences of p140trkA, p145trkB, and p140trkC. Immunoreactivities for trkA and trkB, as well as pantrk, were detected in the developing retina and showed similar distributions. At similar antibody concentrations, trkC immunoreactivity was not detected. In the embryo, immunoreactivities were present in cells located throughout the neuroblastic retina, especially in the inner retinal layers, and in fibers in the nerve fiber layer and optic nerve. In the newborn retina, immunoreactivities for these two receptor isoforms were localized to numerous somata in the inner nuclear layer (INL), as well as to cells in the ganglion cell layer (GCL) and axons in the nerve fiber layer and optic nerve. A similar pattern of immunostaining persisted throughout the first postnatal week. By postnatal day-10, immunostaining was confined to large-diameter cells in the GCL, both heavily stained and lightly stained cells in the INL and a plexus of processes in the inner plexiform layer (IPL). In the adult retina, specific immunoreactivity was present in sparsely distributed, lightly and moderately stained, large cells in the GCL, numerous lightly and moderately stained cells throughout the INL and in plexuses of processes in the IPL and outer plexiform layer. Specific immunostaining of photoreceptor cells was not observed. These observations indicate that high-affinity receptors for the neurotrophins are expressed in cells of the inner retina, including ganglion cells, during the period of retinal development. This is congruent with roles for neurotrophins in such processes as survival, differentiation and synapse formation of cells in the developing visual system.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 1995

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References

Berkemeier, L.R., Winslow, J.W., Kaplan, D.R., Nikolics, K., Goeddel, D.V. & Rosenthal, A. (1991). Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB. Neuron 7, 857866.CrossRefGoogle ScholarPubMed
Bunt, S.M., Lund, R.D. & Land, P.W. (1983). Prenatal development of the optic projection in albino and hooded rats. Developmental Brain Research 6, 149168.CrossRefGoogle Scholar
Carmignoto, G., Maffei, L., Candeo, P., Canella, R. & Comelli, C. (1989). Effect of NGF on the survival or rat retinal ganglion cells following optic nerve section. Journal of Neuroscience 9, 12631272.CrossRefGoogle ScholarPubMed
Carmignoto, G., Comelli, M.C., Candeo, P., Cavicchioli, L., Van, Q., Merighi, A. & Maffei, L. (1991). Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina. Experimental Neurology 111, 302311.CrossRefGoogle ScholarPubMed
Chao, M.V. (1992). Neurotrophin receptors: A window into neuronal differentiation. Neuron 9, 583593.CrossRefGoogle ScholarPubMed
Cordon-Cardo, C., Tapley, P., Jing, S., Nanduri, V., O'Rourke, E., Lamballe, F., Kovary, K., Klein, R., Jones, K.R., Reichardt, L.F. & Barbacid, M. (1991). The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neuro-trophin-3. Cell 66, 173183.Google Scholar
Crespo, D., O'Leary, D.D.M. & Cowan, W.M. (1985). Changes in the numbers of optic nerve fibers during late prenatal and postnatal development in the albino rat. Developmental Brain Research 19, 129134.CrossRefGoogle Scholar
Davies, A.M. (1994). Tracking neurotrophin function. Nature 368, 193194.CrossRefGoogle ScholarPubMed
DiStefano, P.S., Friedman, B., Radziejewski, C., Alexander, C., Boland, P., Schick, C.M., Lindsay, R.M. & Wiegand, S.J. (1992). The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons. Neuron 8, 983993.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, 11401158.CrossRefGoogle ScholarPubMed
Gall, C.M., Gold, S.J., Isackson, P.J. & Seroogy, K.B. (1992). Brainderived neurotrophic factor and neurotrophin-3 mRNAs are expressed in ventral midbrain regions containing dopaminergic neurons. Molecular and Cellular Neuroscience 3, 5663.CrossRefGoogle ScholarPubMed
Garofalo, L., Ribeiro-Da-Silva, A. & Cuello, A.C. (1992). Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proceedings of the National Academy of Sciences of the U.S.A. 89, 26392643.CrossRefGoogle ScholarPubMed
Gotz, R., Lolbeck, R., Lottspeich, F. & Barde, Y.-A. (1992). Production and characterization of recombinant mouse neurotrophin-3. European Journal of Biochemistry 204, 745749.CrossRefGoogle ScholarPubMed
Hempstead, B.L., Dionisio, M.-Z., 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, 678683.CrossRefGoogle ScholarPubMed
Hofer, M.M. & Barde, Y.-A. (1988). Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature 331, 261262.CrossRefGoogle ScholarPubMed
Hohn, A., Leibrock, J., Bailey, K. & Barde, Y.-A. (1990). Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 344, 339341.CrossRefGoogle ScholarPubMed
Ip, N.Y., Ibanez, C.F., Nye, S.H., McClajn, J., Jones, P.P., Gies, D.R., Belluscio, L., LeBeau, M.M., Espinosa, R., Squinto, S.P., Perrson, H. & Yancopoulos, G.D. (1992). Mammalian neuro-trophin-4: Structure, chromosomal localization, tissue distribution, and receptor specificity. Proceedings of the National Academy of Sciences of the U.S.A. 89, 30603064.CrossRefGoogle ScholarPubMed
Jeffery, G. & Perry, V.H. (1982). Evidence for ganglion cell death during development of the ipsilateral retinal projection in the rat. Developmental Brain Research 2, 176180.Google Scholar
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, 30313038.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 kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell 66, 395403.CrossRefGoogle ScholarPubMed
Klein, R., Lamballe, F., Bryant, S. & Barbacid, M. (1992). The trkB tyrosine protein kinase is a receptor for neurotrophin-4. Neuron 8, 947956.Google Scholar
Kondo, Y., Takada, M., Honda, Y. & Mizuno, N. (1993). Bilateral projections of single retinal ganglion cells to the lateral geniculate nuclei and superior colliculi in the albino rat. Brain Research 608, 204215.Google Scholar
Korsching, S., Auburger, G., Heumann, R., Scott, J. & Thoenen, H. (1985). Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO Journal 4, 13891393.Google Scholar
Lam, K., Sefton, A.J. & Bennett, M.R. (1982). Loss of axons from the optic nerve of the rat during early postnatal development. Developmental Brain Research 3, 387491.Google Scholar
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, 967979.CrossRefGoogle ScholarPubMed
Lauterborn, J.C., Issackson, P.J. & Gall, C.M. (1994). Cellular localization of NGF and NT-3 mRNAs in postnatal rat forebrain. Molecular and Cellular Neuroscience 5, 4662.CrossRefGoogle ScholarPubMed
La Vail, M.M., Unoki, K., Yasumura, D., Matthes, M.T., Yancopoulos, G.D. & Steinberg, R.H. (1992). Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proceedings of the National Academy of Sciences of the U.S.A. 89, 1124911253.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, 149152.CrossRefGoogle ScholarPubMed
Lindsay, R.M. & Harmar, A.J. (1989). Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 337, 362364.CrossRefGoogle ScholarPubMed
Lohof, A.M., Ip, N.Y. & Poo, M.-M. (1993). Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 350353.CrossRefGoogle ScholarPubMed
Lund, R.D. & Bunt, A.H. (1976). Prenatal development of central optic pathways in albino rats. Journal of Comparative Neurology 165, 247294.CrossRefGoogle ScholarPubMed
Maisonpierre, P.C., Belluscio, L., Friedman, B., Alderson, F.R., Wlegand, S.J., Furth, M.E., Lindsay, R.M. & Yancopoulos, G.D. (1990 a). NT-3, BDNF, and NGF in the developing rat nervous system: Parallel as well as reciprocal patterns of expression. Neuron 5, 501509.Google Scholar
Maisonpferre, P.C., Belluscio, L., Squinto, S., Ip, N.Y., Furth, M.E., Lindsay, R.M. & Yancopoulos, G.D. (1990 b). Neurotrophin-3: A neurotrophic factor related to NGF and BDNF. Science 247, 14461451.CrossRefGoogle Scholar
Martin-Zanca, D., Highes, S.H. & Barbacid, M. (1986). A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 319, 743748.CrossRefGoogle ScholarPubMed
Perry, V.H., Henderson, Z. & Linden, R. (1983). Postnatal changes in retinal ganglion cell and optic axon populations in the pigmented rat. Journal of Comparative Neurology 219, 356368.CrossRefGoogle ScholarPubMed
Reese, B.E. & Colello, R.J. (1992). Neurogenesis in the retinal ganglion cell layer of the rat. Neuroscience 46, 419429.CrossRefGoogle ScholarPubMed
Richardson, P.M., Issa, V.M.K. & Riopelle, R.J. (1986). Distribution of neuronal receptors for nerve growth factor in the rat. Journal of Neuroscience 6, 23122321.Google Scholar
Rickman, D.W., Lauterborn, J., Brecha, N.C. & Gall, C. (1992). Expression of low-affinity NGF-receptor-immunoreactivity (IR) and BDNF and NT-3 mRNAs in developing rat retina and superior colliculus. Society for Neuroscience Abstracts 18, 225.Google Scholar
Rickman, D.W. & Brecha, N. (1993). Neurotrophin receptor expression in the developing rat retina. Investigative Ophthalmology and Visual Science 34, 878.Google Scholar
Rodriguez-Tébar, A., Jeffery, P.L., Theonen, 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, 296303.CrossRefGoogle ScholarPubMed
Rodriguez-Tébar, A., Dechant, G. & Barde, Y.-A. (1990). Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron 4, 487492.CrossRefGoogle Scholar
Rodriguez-Tébar, A., Dechant, G., Gotz, R. & Barde, Y.-A. (1992). Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO Journal, 11, 917922.Google Scholar
Rodriguez-Tébar, A., Rosa, E. De La & Arribas, A. (1993). Neurotrophin-3 receptors in the developing chicken retina. European Journal of Biochemistry 211, 789794.Google Scholar
Ross, A.H. (1991). Identification of tyrosine kinase Trk as a nerve growth factor receptor. Cell Regulation 2, 685690.CrossRefGoogle ScholarPubMed
Schatteman, G.C., Glbbs, L., Lanahan, A.A., Claude, P. & Bothwell, M. (1988). Expression of NGF receptor in developing and adult primate central nervous system. Journal of Neuroscience 8, 860873.Google Scholar
Sefton, A.J. & Lam, K. (1984). Quantitative and morphological studies on developing optic axons in normal and enucleated albino rats. Experimental Brain Research 57, 107117.CrossRefGoogle ScholarPubMed
Simon, D.K. & O'Leary, D.D.M. (1992). Development of topographic order in the mammalian retinocollicular projection. Journal ofNeu-roscience 12, 12121232.Google ScholarPubMed
Snider, W.D. (1988). Nerve growth factor enhances dendritic arborization of sympathetic ganglion cells in developing mammals. Journal of Neuroscience 8, 26282634.CrossRefGoogle ScholarPubMed
Squinto, S.P., Stitt, T.N., Aldrich, T.H., Davis, S., Bianco, S.M., Radziejewski, C., Glass, D.J., Masiakowski, P., Furth, M.E., Valenzuela, D.M., DeStefano, P.S. & Yancopoulos, G.D. (1991). trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell 65, 885893.CrossRefGoogle Scholar
Takahashi, J.B., Hoshimaru, M., Kikuchi, H. & Hatanaka, M. (1993). Developmental expression of trk B and low-affinity NGF receptor in the rat retina. Neuroscience Letters 151, 174177.Google Scholar
Thoenen, H. (1991). The changing scene of neurotrophic factors. Trends in Neuroscience 14, 165170.Google Scholar
Valenzuela, D.M., Maisonpierre, P.C., Glass, D.J., Rojas, E., Nunez, L., Kong, Y., Cms, D.R., Stitt, T.N., Ip, N.Y. & Yancopoulos, G.D. (1993). Alternative forms of trk C with different functional capabilities. Neuron 10, 963974.Google Scholar
Vedder, H., Affolter, H.-U. & Otten, U. (1993). Nerve growth factor (NGF) regulates tachykinin gene expression and biosynthesis in rat sensory neurons during early postnatal development. Neuropeptides 24, 351357.CrossRefGoogle ScholarPubMed
Yamadori, T., Nakamura, T. & Takami, K. (1989). A study on the retinal ganglion cell which has an uncrossed bifurcating axon in the albino rat. Brain Research 488, 143148.CrossRefGoogle Scholar
Yan, Q. & Johnson, E.M. (1988). An immunohistochemical study of the nerve growth factor receptor in developing rats. Journal of Neuroscience 8, 34813498.Google Scholar
Yhip, J.P.A. & Kirby, M.A. (1990). Topographic organization of the retinocollicular projection in the neonatal rat. Visual Neuroscience 4, 313329.Google ScholarPubMed
Zanellato, A., Comelli, M.C., Dal Toso, R. & Carmignoto, G. (1993). Developing rat retinal ganglion cells express the functional NGF receptor p140trkA. Developmental Biology 159, 105113.CrossRefGoogle ScholarPubMed