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Cell-Specific Gene Expression in Oxytocin and Vasopressin Magnocellular Neurons

  • Chapter
Vasopressin and Oxytocin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 449))

Abstract

The oxytocin (OT) and vasopressin (VP) expressing magnocellular neurons in the hypothalamic-neurohypophysial system (HNS) have been the most studied of all the neuroendocrine cell-types. Despite this, our understanding of the mechanisms that underly the cell-specific expression of the peptide genes in these neurons has remained obscure. Part of the reason for this may be related to the close apposition of the OT and VP genes in the chromosomal locus, the genes being separated by as little as 3.5 kb in the mouse, and their interactions which are critical for cell-specific expression of the genes. Recent studies using intact rat OT and VP constructs in transgenic mice, and rat and mouse VP genes with CAT inserts in exon III as reporters in transgenic rats and mice, respectively, have suggested the presence of cell-specific enhancer elements in the 3’ downstream (intergenic region, IGR) region of the VP gene. Evidence in favor of this view is presented from transgenic mouse studies on the expression of mouse OT- and VP-CAT gene constructs. Oxytocin and vasopressin phenotypes in the magnocellular neuronal population have traditionally been assessed by either immunocytochemical or in situ hybridization histochemical methods leading to the view that these genes are never coexpressed. However, more sensitive methods show that most OT cells also express some VP mRNA, and most VP cells contain some OT mRNA. A third phenotype containing equivalent levels of both OT and VP mRNA can also be found under some conditions, thereby complicating our analysis of cell-specificity. A continuing problem hindering studies of the regulation of OT and VP gene expression in neurons, is the absence of an appropriate cell line to examine these issues. We have found that stationary slice-explant cultures allow for excellent preservation of highly differentiated magnocellular neurons in long-term culture, and that these culture can be used for physiological and pharmacological studies and analysis of gene expression.

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References

  1. Gainer H, Wray S 1994 Cellular and molecular biology of oxytocin and vasopressin. In: Knobil E Neill D (eds) The Physiology of Reproduction, 2nd edition, New York, Raven Press, pp 1099–1129.

    Google Scholar 

  2. Burbach JPH, van Shaick HSA, deBree FM, Lopes da Silva S, Adan RAH 1995 Functional domains in the oxytocin gene for regulation of expression and biosynthesis of gene products. In: Ivell R, Russell J (eds) Oxytocin, Plenum Press, NY pp 9–21.

    Google Scholar 

  3. Burbach JPH, this volume.

    Google Scholar 

  4. Bamberger AM, Pu L-P, Cool DR, Loh YP 1995 The neuro-2a neuroblastoma cell line expresses [Met]enkephalin and vasopressin mRNA and peptide. Mol Cell Endocrinol 13:155–163.

    Article  Google Scholar 

  5. Kai-Kai MA, Anderton BH, Keen P 1986 A quantitative analysis of the interrelationships between sub-populations of rat sensory neurons containing arginine vasopressin or oxytocin and those containing substance P, fluoride-resistant acid phosphatase or neurofilament protein. Neuroscience 18:475–486.

    Article  PubMed  CAS  Google Scholar 

  6. Jessell TM, Dodd J 1986 Neurotransmitters and differentiation antigens in subsets of sensory neurons projecting to the spinal dorsal horn. In: Martin JB, Barchas JD (eds) Neuropeptides in Neurologic and psychiatric Disease, Raven Press, NY pp 111–133.

    Google Scholar 

  7. Kai-Kai MA, Che Y-M 1995 Distribution of arginine-vasopressin in the trigeminal, dorsal root ganglia and spinal cord of the rat; depletion by capsacin. Comp Biochem Physiol 110A:71–78.

    Article  CAS  Google Scholar 

  8. Goldstein ME, House SB, Gainer H 1991 NF-L and peripherin immunoreactivities define distinct classes of rat sensory ganglion cells. J Neurosci Res 30:92–104.

    Article  PubMed  CAS  Google Scholar 

  9. Hallbeck M, Hermanson O, Blonquist A 1996 Preprovasopressin mRNA is not present in dorsal root ganglia of rat. Neuroscience Letters 209:125–128.

    Article  PubMed  CAS  Google Scholar 

  10. tiara Y, Battey J, Gainer H 1990 Structure of mouse vasopressin and oxytocin genes. Mol Brain Res 8:319–324.

    Article  Google Scholar 

  11. Ratty A, Jeong S-W, Nagle JW, Chin H, Gainer H, Murphy D, Venkatesh B 1996 A systematic survey of the intergenic region between the murine oxytocin and vasopressin encoding genes. Gene 174:71–78.

    Article  PubMed  CAS  Google Scholar 

  12. Mohr E, Schmitz E, Richter D 1988 A single rat genomic DNA fragment encodes both the oxytocin and vasopressin genes separated by Il kilobases and oriented in oposite transcriptional directions. Biochimie 70:649–654.

    Article  PubMed  CAS  Google Scholar 

  13. Gainer H, Jeong S-W, Witt DM, Chin H 1995 Strategies for cell biological studies in oxytocinergic neurons. In: Ivell R, Russell J (eds) Oxytocin, Plenum Press, NY pp 1–8.

    Google Scholar 

  14. Young WS III, Reynolds K, Shepard EA, Gainer H, Castel M 1990 Cell-specific expression of the rat oxytocin gene in transgenic mice. J Neuroendocrinol 2:917–925.

    Article  PubMed  CAS  Google Scholar 

  15. Belenky M, Castel M, Young WS III, Gainer H, Cohen S 1992 Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene. Brain Res 583:279–286.

    Article  PubMed  CAS  Google Scholar 

  16. Grant FD, Reventos J, Gordon JW, Kawabata S, Miller M, Majoub JA 1993 Expression of the rat arginine vasopressin gene in transgenic mice. Mol Endocrinol 7:659–667.

    Article  PubMed  CAS  Google Scholar 

  17. Zeng Q, Carter DA, Murphy D 1994 Cell specific expression of a vasopressin transgene in rats. J Neuroendocrinol 6:469–477.

    Article  PubMed  CAS  Google Scholar 

  18. Waller S, Fairhall KM, Xu J, Robinson ICAF, Murphy D 1996 Neurohypophyseal and fluid homeostasis in transgenic rats expressing a tagged vasopressin prepropeptide in hypothalamic neurons. Endocrinology 137:5068–5077.

    Article  PubMed  CAS  Google Scholar 

  19. Jirikowki G, Reisert I, Pilgrim CH 1981 Neuropeptides in dissociated cultures of hypothalamus and sep-turn. Quantitation of immunoreactive neurons. Neuroscience 6:1953–1960.

    Article  Google Scholar 

  20. DiScala, Guenot D, Strosser MT, Sarlieve LL, Legros JJ, Richard P 1990 Development of neurophysincontaining neurons in primary cultures of rat hypothalami is related to the age of the embryo: Morphological study and comparison of in vivo and in vitro neurophysins, oxytocin, and vasopressin content J Neurosci Res 25:94–102.

    Google Scholar 

  21. Oeding P, Schilling K, Schmale H 1990 Vasopressin expression in cultured neurons is stimulated by cyclic AMP. J Neuroendocrinol 2:859–865.

    Article  CAS  Google Scholar 

  22. Sladek CD, Gallagher MJ 1993 The stimulation of vasopressin gene expression in cultured hypothalamic neurons by cyclic adenosine 3’ 5’-monophosphate is reversible. Endocrinology 133:1320–1330.

    Article  PubMed  CAS  Google Scholar 

  23. Mathiasen JR, Larson ER, Ariano MA, Sladek CD 1996 Neurophysin expression is stimulated by dopamine D1 agonist in dispersed hypothalamic cultures. Am J Physiol 270:R404–R412.

    PubMed  CAS  Google Scholar 

  24. Clarke MJO, Lowry P, Gillies G 1987 Assessment of corticotropin-releasing factor, vasopressin, and somatostatin secretion by fetal hypothalamic neurons in culture. Neuroendocrinology 46:147–154.

    Article  PubMed  CAS  Google Scholar 

  25. Bennett BA, Sundberg DK, Morris M 1990 Evaluation of catecholaminergic activity in hypothalamic cultures. Methods in Neurosciences 2:330–341.

    Google Scholar 

  26. Yamashita N, Nishiyama N, Abe K, Saito H, Fukuda J 1992 Primary culture of postnatal rat hypothalamic neurons in astrocyte-conditioned medium Brain Research 594:215–220.

    CAS  Google Scholar 

  27. Bilinski M, Sanchez A, Nicolini VG, Villar MJ, Tramezzani JH 1996 Dispersion and culture of magnocellular neurons from the supraoptic nucleus of the adult rat. J Neuroscience Methods 64:13–18.

    Article  CAS  Google Scholar 

  28. Gahwiler BH 1988 Organotypic cultures of neural tissue. Trends Neurosci 11:484–489.

    Article  PubMed  CAS  Google Scholar 

  29. Gahwiler BH 1981 Organotypic monolayer cultures of nervous tissue. J Neursci 4:329–342.

    CAS  Google Scholar 

  30. Gahwiler BH, Capogna M, Debanne D, McKinney RA, Thompson SM 1997 Organic slice cultures: a technique has come of age. Trends Neurosci 20:471–477.

    Article  PubMed  CAS  Google Scholar 

  31. Wray S, Gahwiler BH, Gainer H 1988 Slice cultures of LHRH neurons in the presence and absence of brainstem and pituitary. Peptides 9:1151–1175.

    Article  PubMed  CAS  Google Scholar 

  32. Wray S, Castel M, Gainer H 1993 Characterization of the suprachiasmatic nucleus in organotypic slice ex-plant cultures. Microsc Res Tech 25:46–80.

    Article  PubMed  CAS  Google Scholar 

  33. Gainer H, Kusano K, Wray S 1993 Hypothalamic slice-explant cultures as models for the longterm study of gene expression and cellular activity. Regulatory Peptides 45:25–29.

    Article  PubMed  CAS  Google Scholar 

  34. Bertini LT, Kursner C, Gaillard RC, Corder R, Kiss JZ 1993 A tissue culture model of the hypophysiotrophic CRF producing neuronal system. Neuroendocrinology 57:716–728.

    Article  PubMed  CAS  Google Scholar 

  35. Stoppini L, Buchs PA, Muller D 1991 A simple method for organotypic cultures of nervous system. J Neurosci Methods 37:173–182.

    Article  PubMed  CAS  Google Scholar 

  36. Belenky M, Wagner S, Yarom Y, Matzner H, Cohen S, Castel M 1995 The suprachiasmatic nucleus in stationary organotypic culture. Neuroscience 70:127–143.

    Article  Google Scholar 

  37. House SB, Thomas A, Kusano K, Gainer H 1996 Stationary organotypic cultures of rodent hypothalamic oxytocin and vasopressin neurons. Society for Neuroscience 26th Annual Meeting 22:156.4 (Abstract).

    Google Scholar 

  38. Arnold D, Feng L, Kim J, Heintz N 1994 A strategy for the analysis of gene expression during neural development. Proc Natl Acad Sci USA 91:9970–9974.

    Article  PubMed  CAS  Google Scholar 

  39. Lo DC, McAllister AK, Katz LC 1994 Neuronal transfection in brain slices using particle-mediated gene transfer. Neuron 13:1263–1268.

    Article  PubMed  CAS  Google Scholar 

  40. McAllister AK, Lo DC, Katz LC 1995 Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 15:791–803.

    Article  PubMed  CAS  Google Scholar 

  41. Arnold DB, Heintz N 1997 A calcium responsive element that regulates expression of two calcium binding proteins in purkinje cells. Proc Natl Acad Sci USA 94:8842–8847.

    Article  PubMed  CAS  Google Scholar 

  42. Thomas A, House S,Jeong S W, Fields R, Gainer H 1997 Analysis of Oxytocin and Vasopressin Gene Expression in Hypothalamic Organotypic Cultures. World Congress of Neurohypophysial Hormones Meeting, Abstract #67.

    Google Scholar 

  43. Karpati G, Lochuller H, Nalbantoglu J, Durham H 1996 The principles of gene therapy for the nervous system. Trends in Neuroscience 19:49–54.

    Article  CAS  Google Scholar 

  44. Slack RS, Miller FD 1996 Viral vectors for modulating gene expression in neurons. Current Opinion in Neurobiology 6:576–583.

    Article  PubMed  CAS  Google Scholar 

  45. Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O’Malley KL, During MJ 1994 Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nature Genetics 8:148–154.

    Article  PubMed  CAS  Google Scholar 

  46. Geddes BJ, Harding TC, Hughes DS, Byrnes AP, Lightman SL, Conde G, Uney JB 1996 Persistent trans-gene expression in the hypothalamus following stereotaxic delivery of a recombinant adenovirus: Supression of the immune response with cyclosporin. Endocrinology 137:5166–5169.

    Article  PubMed  CAS  Google Scholar 

  47. Wu P, Du B, Phillips MI, Terwilliger FF 1996 Efficient and long-term gene delivery into rat brain using adeno-associated viral vectors. Soc for Neurosciences 26th Annual Meeting 22:133.2 (Abstract).

    Google Scholar 

  48. Xiao X, deVlaminck W, Monahan J 1993 Adenoassociated virus (AAV) vectors for gene transfer. Advanced Drug Delivery Reviews 12:201–215.

    Article  CAS  Google Scholar 

  49. Eberwine J, Yeti H, Miyashiro K, Cao Y, Nair S, Finnell R, Zettel M, Coleman, P 1992 Analysis of gene expression in single live neurons. Proc Natl Acad Sci USA 89:3010–3014.

    Article  PubMed  CAS  Google Scholar 

  50. Mackler SA, Eberwine J 1993 Diversity of glutamate receptor subunit mRNA expression within live hippocampal CAI neurons. Molecular Pharmacology 44:308–315.

    PubMed  CAS  Google Scholar 

  51. Korneev S, Blackshaw SE, Kaiser K, Davies JA 1996 cDNA libraries from identified neurons. Proc R Soc Lond B 263:57–62.

    Article  CAS  Google Scholar 

  52. Merz DC, Dunn RJ, Drapeau P 1995 Generating a phage display antibody library against an identified neuron. J Neuroscience Methods 62:213–219.

    Article  CAS  Google Scholar 

  53. Dulac C, Axel R 1995 A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206.

    Article  PubMed  CAS  Google Scholar 

  54. Armstrong WE 1995 Morphhological and electrophysiological classification of hypothalamic supraoptic neurons. Prog in Neurobiology 47:291–339.

    CAS  Google Scholar 

  55. Villar MJ, Meister B, Cortes R, Schalling M, Morris M, Hokfelt T 1990 Neuropeptide gene expression in hypothalamic magnocellular neurons of normal and hypophysectomized rats: a combined immunohistochemical and in situ hybridization study. Neuroscience 36:181–199.

    Article  PubMed  CAS  Google Scholar 

  56. Meister B 1993 Gene expression and chemical diversity in hypothalamic neurosecretory neurons. Molecular Neurobiology 7: 87–110.

    Article  PubMed  CAS  Google Scholar 

  57. Mohr E, Bahnsen U, Kiessling C, Richter D 1988 Expression of the vasopressin and oxytocin genes in rats occurs in mutually exclusive sets of hypothalamic neurons. FEBS Letters 242:144–148.

    Article  PubMed  CAS  Google Scholar 

  58. Kiyama H, Emson PC 1990 Evidence for the coexpression of oxytocin and vasopressin messenger ribonucleic acids in magnocellular neurosecretory cells: simultaneous demonstration of two neurophysin messenger ribonucleic acids by hybridization histochemistry. J Neuroendocrinol 2:257–259.

    Article  PubMed  CAS  Google Scholar 

  59. Mezey E, Kiss JZ 1991 Coexpression of vasopressin and oxytocin in hypothalamic supraoptic neurons of lactating rats. Endocrinology 129:1814–1820.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Laboratory of Neurochemistry, National Institutes of Health, NINDS, Building 36, Room 4D20, Bethesda, Maryland, 20892, USA

    Harold Gainer

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  1. Harold Gainer
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Editors and Affiliations

  1. McGill University, Montreal, Quebec, Canada

    Hans H. Zingg  & Charles W. Bourque  & 

  2. University of Montreal, Montreal, Quebec, Canada

    Daniel G. Bichet

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Gainer, H. (1998). Cell-Specific Gene Expression in Oxytocin and Vasopressin Magnocellular Neurons. In: Zingg, H.H., Bourque, C.W., Bichet, D.G. (eds) Vasopressin and Oxytocin. Advances in Experimental Medicine and Biology, vol 449. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4871-3_2

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  • DOI: https://doi.org/10.1007/978-1-4615-4871-3_2

  • Publisher Name: Springer, Boston, MA

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