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Effects of cell signaling on the development of GABA receptors in chick retina neurons

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Abstract

R-cognin, a cell recognition molecule, and insulin are known to play significant roles in GABAergic differentiation in the developing chick retina. In the present study, the effects of insulin and R-cognin on post-synaptic (GABAceptive) differentiation were investigated. In ovo binding of [3H]GABA and [3H]flunitrazepam ([3H]Flu) to the GABA and benzodiazepine (BZD) receptors, respectively, remained at low levels during early embryogenesis but increased sharply from mid-embryogenesis through hatching, increases which also occur in cultured neurons from early-embryonic (E7) and mid-embryonic (E11) chick retina. E7 neurons respond to insulin treatment (100 ng/ml) with increased [3H]Flu binding but no change in [3H]GABA binding. Cognin antibody (10 μg/ml) treatment of E7 neurons caused no significant inhibition of the developmental increases in binding of either radioligand. Insulin in E11 cultures led to greater developmental increases in binding sites for both radioligands, but exposure to cognin antibody was without significant effect. These data, along with previous studies, indicate that GABAergic differentiation in developing chick retina is regulated, in part, by insulin and cognin-mediated cell signaling. Insulin also regulates post-synaptic (GABAceptive) differentiation whereas cognin-mediated interactions are relatively insignificant.

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Abbreviations

BZD:

benzodiazepine

ChAT:

choline acetyltransferase

Flu:

flunitrazepam

GABA:

γ-aminobutyric acid

GAD:

glutamate decarboxylase (glutamic acid decarboxylase)

References

  1. Hausman, R. E., Sagar, G. D. V., and Shah, B. H. 1991. Initial cholinergic differentiation in embryonic chick retina is responsive to insulin and cell-cell interactions. Dev. Brain Res. 59:31–37.

    Google Scholar 

  2. Peterson, S. W., Kyriakis, J. M., and Hausman, R. E. 1986. Changes in insulin binding to developing embryonic chick neural retina cells. J. Neurochem. 47:851–855.

    PubMed  Google Scholar 

  3. De Pablo, F., Scott, L. A., and Roth, J. 1990. Insulin and insulinlike growth factor I in early development: Peptides, receptors and biological events. Endocr. Rev., 11:558–577.

    PubMed  Google Scholar 

  4. Meimaridis, D. G., Morse, D. E., Pansky, B., and Budd, G. C. 1990. Insulin immunoreactivity in the fetal and neonatal rat retina. Neurosci. Lett. 118:116–119.

    PubMed  Google Scholar 

  5. Waldbillig, R. J., Arnold, D. R., Fletcher, R. T., and Chader, G. J. 1991. Insulin and IGF-I binding in developing chick neural retina and pigment epithelium: A characterization of binding and structural differences. Exp. Eye Res. 53:13–22.

    PubMed  Google Scholar 

  6. Kyriakis, J. M., Hausman, R. E., and Peterson, S. W. 1987. Insulin stimulates choline acetyltransferase in the ganglion cell layer of developing chick neural retina. Proc. Natl. Acad. Sci. USA 84:7463–7467.

    PubMed  Google Scholar 

  7. Shah, B. H., and Hausman, R. E. 1993. Effect of insulin on GABAergic development in the embryonic chick retina. Develop. Brain Res. (in press).

  8. Hausman, R. E., and Moscona, A. A. 1975. Purification and characterization of the neural retina cell aggregating factor. Proc. Natl. Acad. Sci. USA 72:916–920.

    PubMed  Google Scholar 

  9. Hausman, R. E., and Moscona, A. A. 1976. Isolation of retinaspecific cell aggregating factor from membranes of embryonic retina tissue. Proc. Natl. Acad. Sci. USA 73:3594–3598.

    PubMed  Google Scholar 

  10. Dobi, E. T., Troccoli, N. M., and Hausman, R. E. 1986. Distribution of R-cognin in late embryonic and post-hatching chick retina. Invest. Ophthalmol. Vis. Sci. 27:323–329.

    PubMed  Google Scholar 

  11. Dobi, E. T., Naya, F. J., and Hausman, R. E. 1988. Distribution of R-cognin and choline acetyltransferase in the ganglion cell layer of developing chick neural retina. Cell Differ. 22:115–124.

    PubMed  Google Scholar 

  12. Sagar, G. D. V., Krishna Rao, A. S. M., Ren, Y., and Hausman, R. E. 1992. The cell recognition molecule, cognin, mediates choline acetyltransferase activity in embryonic chick retina. Brain Res. 585:63–70.

    PubMed  Google Scholar 

  13. Shah, B. H., Krishna Rao, A. S. M., and Hausman, R. E. 1992. Role of the cell recognition molecule cognin, in GABAergic differentiation in chick retina. Brain Res. 589:268–274.

    PubMed  Google Scholar 

  14. De Blas, A. L., Vitorica, J., and Friedrich, P. 1986. Localization of the GABA-A receptor in the rat brain with a monoclonal antibody to the 57,000 Mr peptide of the GABA-A receptor/benzodiazepine receptor/Cl channel complex. J. Neurosci. 8:602–614.

    Google Scholar 

  15. Vitorica, J., Park, D., Chin, G., and De Blas, A. L. 1988. Monoclonal antibodies and conventional antisera to the GABAA receptor/benzodiazepine receptor/Cl channel complex. J. Neurosci. 8:615–622.

    PubMed  Google Scholar 

  16. Ewert, M., De Blas, A. L., Möhler, H., and Seeburg, P. H. 1992. A prominent epitope on GABAA receptors is recognized by two different monoclonal antibodies. Brain Res. 569:57–62.

    PubMed  Google Scholar 

  17. Hausman, R. E., and Moscona, A. A. 1973. Cell surface interactions: Inhibition by proflavine of embryonic cell aggregation and the production of specific cell aggregating factor. Proc. Natl. Acad. Sci. USA. 70:3111–3114.

    PubMed  Google Scholar 

  18. Hausman, R. E., Katz, M. S., Dobi, E. T., and Offermann, J. 1986. Cognin distribution during differentiation of embryonic chick retinal cells in vitro. Int. J. Devel. Neurosci. 4:537–544.

    Google Scholar 

  19. Hausman, R. E., and Moscona, A. A. 1979. Immunologic detection of retina cognin on the surface of embryonic cells. Exp. Cell. Res. 119:191–204.

    PubMed  Google Scholar 

  20. Mehta, A. K., and Ticku, M. K. 1988. Developmental aspects of benzodiazepine receptors and GABA-gated chloride channels in primary cultures of spinal cord neurons. Brain Res. 454:156–163.

    PubMed  Google Scholar 

  21. Hablitz, J. J., Tehrani, M. H. J., and Barnes, E. M. Jr. 1989. Chronic exposure of developing cortical neurons to GABA downregulates GABA/benzodiazepine receptors and GABA-gated chloride channels. Brain Res. 501:332–338.

    PubMed  Google Scholar 

  22. Lloyd, K. G. 1986. GABA receptor binding, Pages 217–249,in A. A. Boulton, G. B. Baker, and P. D. Hrdina (eds), Neuromethods 4. Receptor Binding, Humana Press, Clifton, NJ.

    Google Scholar 

  23. Lewin, L., Mattsson, M.-O., and Sellström, Å. 1992. Inhibition of transporter mediated gamma-aminobutyric acid (GABA) release by SKF 89976-A, a GABA uptake inhibitor, studied in a primary neuronal culture from chicken. Neurochem. Res. 17:577–584.

    PubMed  Google Scholar 

  24. Morgan, W. W. 1985. GABA: A potential neurotransmitter in retina, pp. 63–96,in W. W. Morgan (ed) Retinal transmitters and modulators: models for the brain. CRC Press, Boca Raton.

    Google Scholar 

  25. Scatchard, B. 1949. The attraction of proteins for small molecular ions. Ann. NY Acad. Sci. 51:660–672.

    Google Scholar 

  26. Sambrook, J., Fritsch, E. F., and Maniatis, T. 1989. Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. R1-R4.

    Google Scholar 

  27. Tehrani, M. H. J., and Barnes, E. M. jr. 1986. Ontogeny of the GABA receptor complex in chick brain: studies in vivo and in vitro. Dev. Brain Res. 25:91–98.

    Google Scholar 

  28. Gravielle, M. C., and De Plazas, S. F. 1991. Benzodiazepine receptor sites in the chick optic lobe: development and pharmacological characterization. Neurochem. Res. 16:57–62.

    PubMed  Google Scholar 

  29. Yazulla, S., Studholme, K. M., Vitorica, J., and De Blas, A. L. 1989. Immunocytochemical localization of GABAA receptors in goldfish and chicken retinas. J. Comp. Neurol. 280:15–26.

    PubMed  Google Scholar 

  30. Jong, Y.-F., Thamphy, K. G., and Barnes, E. M. jr. 1986. Ontogeny of GABAergic neurons in chick brain. Dev. Brain Res. 25:83–90.

    Google Scholar 

  31. Kuriyama, K., Tomono, S., Kishi, M., Mukainaka, T., and Ohkuma, S. 1987. Development of γ-aminobutyric (GABA)ergic neurons in cerebral cortical neurons in primary culture. Brain Res. 416:7–21.

    PubMed  Google Scholar 

  32. Barnes, E. M. jr. 1989. The biochemical development of GABA transmission, Pages 186–197,in P. Kellway and J. L. Noebels, (eds), Problems and Concepts in Developmental Neurophysiology, Johns Hopkins University Press, Baltimore.

    Google Scholar 

  33. Gonzàlez, N. N., Alfie, J., and De Plazas, S. F. 1990. Glutamic acid decarboxylase in different areas of the developing chick central nervous system. Neurochem. Res. 15:917–921.

    PubMed  Google Scholar 

  34. Vitorica, J., Park, D., Chin, G., and De Blas, A. L. 1990. Characterization with antibodies of the γ-aminobutyric acidA/benzodiazepine receptor complex during development of the rat brain. J. Neurochem. 54:187–194.

    PubMed  Google Scholar 

  35. Alstein, M., Dudai, Y., and Vogel, Z. 1981. Benzodiazepine receptors in chick retina: development and cellular localization. Brain Res. 206:198–202.

    PubMed  Google Scholar 

  36. Coyle, J. T., and Enna, S. J. 1976. Neurochemical aspects of the ontogenesis of GABAergic neurons in the rat brain. Brain Res. 115:174–178.

    PubMed  Google Scholar 

  37. Hausman, R. E. 1988. Retina cognin and cell differentiation, Pages 133–150,in S. R. Hilfer and J. B. Sheffield (eds), Cell interactions in visual development, Cell and Developmental Biology of the Eye. Proceedings of the 11th Symposium on Ocular Biology and Visual Development, Springer-Verlag, New York.

    Google Scholar 

  38. Sheffield, J. B., and Fischman, D. A. 1970. Intercellular junctions in the developing neural retina of chick embryos. Z. Zellforsch. 104:405–418.

    PubMed  Google Scholar 

  39. Meinecke, D. L., and Rakic, P. 1990. Developmental expression of GABA and subunits of the GABAA receptor complex in an inhibitory synaptic circuit in the rat cerebellum. Dev. Brain Res. 55:73–86.

    Google Scholar 

  40. Gambarana, C., Pittman, R., and Siegel, R. E. 1990. Developmental expression of the GABAA receptor α1 subunit mRNA in the rat brain. J. Neurobiol. 21:1169–1179.

    PubMed  Google Scholar 

  41. Frostholm, A., Zdilar, D., Chang, A., and Rotter, A. 1991. Stability of GABAA/benzodiazepine receptor α1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development. Dev. Brain Res. 64:121–128.

    Google Scholar 

  42. Prichett, D., Sontheimer, H., Shivers, B. D., Ymer, S., Kettenman, H., Schofield, P. R., and Seeburg, P. 1989. Importance of a novel GABA-A receptor subunit for benzodiazepine pharmacology. Nature 338:582–585.

    PubMed  Google Scholar 

  43. Zdilar, D., Rotter, A., and Frostholm, A. 1991. Expression of GABAA/benzodiazepine receptor α1-subunit nRNA and [3H] flunitrazepam binding sites during postnatal development of mouse cerebellum. Dev. Brain Res. 61:63–71.

    Google Scholar 

  44. Vitorica, J., Park, D., and De Blas, A. L. 1990. The GABAA/benzodiazepine receptor complex in rat brain neuronal cultures. Characterization by immunoprecipitation. Brain Res. 537:209–215.

    PubMed  Google Scholar 

  45. De Mello, F. G., Bachrach, U., and Nirenberg, M. 1976. Ornithine and glutamic acid decarboxylase activities in the developing chick retina. J. Neurochem. 7:847–851.

    Google Scholar 

  46. Gleason, E., and Wilson, M. 1991. Chemical and electrical synapses formed by chick retinal neurons maintained in dissociated cell culture. Soc. Neurosci Abs. 1566.

  47. Huba, R., and Hofmann, H.-D. 1990. Identification of GABAergic amacrine cell-like neurons developing in chick retinal monolayer cultures. Neurosci. Lett. 117:37–42.

    PubMed  Google Scholar 

  48. Erdo, S. L., and Wolff, J. R. 1990. Gamma-aminobutyric acid outside the mammalian brain. J. Neurochem. 54:363–372.

    PubMed  Google Scholar 

  49. Meier, E., Hertz, L., and Schousboe, A. 1991. Neurotransmitters as developmental signals. Neurochem. Int. 19:1–15.

    Google Scholar 

  50. Wolff, J. R., Joo, F., and Dames, W. 1978. Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat. Nature 274:72–74.

    PubMed  Google Scholar 

  51. Wolff, J. R., Joo, F., Dames, W., and Feher, O. 1979. Induction and maintenance of free postsynaptic membrane thickenings in the adult superior cervical ganglion. J. Neurocytol. 8:549–563.

    PubMed  Google Scholar 

  52. Belhage, B., Damgaard, I., Saederup, E., Squires, R. F., and Schousboe, A. 1991. High- and low-affinity GABA-receptors in cultured cerebellar granule cells regulate transmitter release by different mechanisms. Neurochem. Int. 19:475–482.

    Google Scholar 

  53. Meier, E., Drejer, J., and Schousboe, A. 1984. The trophic effect of GABA on cerebellar granule cells is mediated by GABA-receptors. Int. J. Dev. Neurosci. 3:401–407.

    Google Scholar 

  54. Morgan, W. W., and Kamp, C. W. 1985. The demonstration of benzodiazepine binding sites and of pharmacologic effects of benzodiazepines in retina, Pages 97–106.in W. W. Morgan (ed), Retinal transmitters and modulators: models for the brain. CRC Press, Boca Raton.

    Google Scholar 

  55. Yazulla, S., and Brecha, N. 1981. Localized binding of 3H-muscimol to synapses in the chick retina. Proc. Natl. Acad. Sci. USA 78:643–647.

    PubMed  Google Scholar 

  56. Young, W. S. III, and Kuhar, M. J. 1979. Autoradiographic localization of benzodiazepine receptors in the brains of humans and animals. Nature 280:393–396.

    Google Scholar 

  57. Brecha, N. C., Sternini, C., and Humphrey, M. F. 1991. Cellular distribution ofl-glutamate decarboxylase (GAD) and gamma-aminobutyric acidA (GABAA) receptor mRNAs in the retina. Cell. Mol. Neurobiol. 11:497–509.

    PubMed  Google Scholar 

  58. Tehrani, M. H. J., and Barnes, E. M., Jr. 1991. Agonist-dependent internalization of gamma-aminobutyric acidA/benzodiazepine receptors in chick cortical neurons. J. Neurochem. 57:1307–1312.

    PubMed  Google Scholar 

  59. Montpied, P., Ginns, E. I., Martin, B. M., Roca, D., Farb, D. H., and Paul, S. M. 1991. Gamma-aminobutyric acid (GABA) induces a receptor-mediated reduction in GABAA receptor α subunit messenger RNAs in embryonic chick neurons in culture. J. Biol. Chem. 266:6011–6014.

    PubMed  Google Scholar 

  60. Tehrani, M. H. J., and Barnes, E. M., Jr. 1988. GABA downregulates the GABA/benzodiazepine receptor complex in developing cerebral neurons. Neurosci. Lett. 87:288–292.

    PubMed  Google Scholar 

  61. Woods, J. D., and Davies, M. 1989. Regulation of the γ-aminobutyric acid receptor by γ-aminobutyric acid levels within the postsynaptic cell. J. Neurochem. 53:1648–1651.

    PubMed  Google Scholar 

  62. Woods, J. D., and Davies, M. 1991. Regulation of the GABA-A receptor/ion channel complex by intracellular GABA levels. Neurochem. Res. 16:375–379.

    PubMed  Google Scholar 

  63. Yang, C.-Y., Lin, Z.-S., and Yazulla, S. 1992. Localization of GABAA receptor subtypes in the tiger salamander retina. Visual Neurosci. 8:57–64.

    Google Scholar 

  64. Krishna Rao, A. S. M., and Hausman, R. E. 1991. Chiek retina cell recognition protein, cognin, is a multifunctional enzyme. J. Cell Biol. 115:70a.

    Google Scholar 

  65. Krishna Rao, A. S. M., and Hausman, R. E. 1992. Characterization of cDNA for the cell recognition molecule, R-cognin: homology with a multifunctional protein. Proc. Natl. Acad. Sci. USA 90 (in press).

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Shah, B.H., Hausman, R.E. Effects of cell signaling on the development of GABA receptors in chick retina neurons. Neurochem Res 18, 957–964 (1993). https://doi.org/10.1007/BF00966753

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