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. 1976 Feb 1;68(2):173–188. doi: 10.1083/jcb.68.2.173

Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation

PMCID: PMC2109636  PMID: 1245547

Abstract

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight- junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin- A chick-skin system is presented as a responsive model for the controlled study of junction assembly.

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Selected References

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  1. Albertini D. F., Anderson E. Structural modifications of lutein cell gap junctions during pregnancy in the rat and the mouse. Anat Rec. 1975 Feb;181(2):171–194. doi: 10.1002/ar.1091810203. [DOI] [PubMed] [Google Scholar]
  2. Albertini D. F., Anderson E. The appearance and structure of intercellular connections during the ontogeny of the rabbit ovarian follicle with particular reference to gap junctions. J Cell Biol. 1974 Oct;63(1):234–250. doi: 10.1083/jcb.63.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albertini D. F., Fawcett D. W., Olds P. J. Morphological variations in gap junctions of ovarian granulosa cells. Tissue Cell. 1975;7(2):389–405. doi: 10.1016/0040-8166(75)90014-2. [DOI] [PubMed] [Google Scholar]
  4. Benedetti E. L., Dunia I., Bloemendal H. Development of junctions during differentiation of lens fibers. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5073–5077. doi: 10.1073/pnas.71.12.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bennett M. V. Function of electrotonic junctions in embryonic and adult tissues. Fed Proc. 1973 Jan;32(1):65–75. [PubMed] [Google Scholar]
  6. Bonanni F., De Luca L. Vitamin A-dependent fucose-glycopeptide from rat tracheal epithelium. Biochim Biophys Acta. 1974 May 24;343(3):632–637. doi: 10.1016/0304-4165(74)90282-7. [DOI] [PubMed] [Google Scholar]
  7. Chalcroft J. P., Bullivant S. An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture. J Cell Biol. 1970 Oct;47(1):49–60. doi: 10.1083/jcb.47.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Claude P., Goodenough D. A. Fracture faces of zonulae occludentes from "tight" and "leaky" epithelia. J Cell Biol. 1973 Aug;58(2):390–400. doi: 10.1083/jcb.58.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Luca L., Wolf G. Mechanism of action of vitamin A in differentiation of mucus-secreting epithelia. J Agric Food Chem. 1972 May-Jun;20(3):474–476. doi: 10.1021/jf60181a034. [DOI] [PubMed] [Google Scholar]
  10. DeLuca L., Yuspa S. H. Altered glycoprotein synthesis in mouse epidermal cells treated with retinyl acetate in vitro. Exp Cell Res. 1974 May;86(1):106–110. doi: 10.1016/0014-4827(74)90654-5. [DOI] [PubMed] [Google Scholar]
  11. Decker R. S., Friend D. S. Assembly of gap junctions during amphibian neurulation. J Cell Biol. 1974 Jul;62(1):32–47. doi: 10.1083/jcb.62.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dodson J. W. The differentiation of epidermis. II. Alternative pathways of differentiation of embryonic chicken epidermis in organ culture. J Embryol Exp Morphol. 1967 Feb;17(1):107–117. [PubMed] [Google Scholar]
  13. Elias P. M., Friend D. S. The permeability barrier in mammalian epidermis. J Cell Biol. 1975 Apr;65(1):180–191. doi: 10.1083/jcb.65.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. FARQUHAR M. G., PALADE G. E. Junctional complexes in various epithelia. J Cell Biol. 1963 May;17:375–412. doi: 10.1083/jcb.17.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. FELL H. B., MELLANBY E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J Physiol. 1953 Mar;119(4):470–488. doi: 10.1113/jphysiol.1953.sp004860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Friend D. S., Gilula N. B. Variations in tight and gap junctions in mammalian tissues. J Cell Biol. 1972 Jun;53(3):758–776. doi: 10.1083/jcb.53.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Frömter E., Diamond J. Route of passive ion permeation in epithelia. Nat New Biol. 1972 Jan 5;235(53):9–13. doi: 10.1038/newbio235009a0. [DOI] [PubMed] [Google Scholar]
  18. Furshpan E. J., Potter D. D. Low-resistance junctions between cells in embryos and tissue culture. Curr Top Dev Biol. 1968;3:95–127. doi: 10.1016/s0070-2153(08)60352-x. [DOI] [PubMed] [Google Scholar]
  19. Goodenough D. A., Gilula N. B. The splitting of hepatocyte gap junctions and zonulae occludentes with hypertonic disaccharides. J Cell Biol. 1974 Jun;61(3):575–590. doi: 10.1083/jcb.61.3.575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Goodenough D. A., Revel J. P. A fine structural analysis of intercellular junctions in the mouse liver. J Cell Biol. 1970 May;45(2):272–290. doi: 10.1083/jcb.45.2.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Goodenough D. A., Stoeckenius W. The isolation of mouse hepatocyte gap junctions. Preliminary chemical characterization and x-ray diffraction. J Cell Biol. 1972 Sep;54(3):646–656. doi: 10.1083/jcb.54.3.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johnson R., Hammer M., Sheridan J., Revel J. P. Gap junction formation between reaggregated Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4536–4540. doi: 10.1073/pnas.71.11.4536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kanai M., Raz A., Goodman D. S. Retinol-binding protein: the transport protein for vitamin A in human plasma. J Clin Invest. 1968 Sep;47(9):2025–2044. doi: 10.1172/JCI105889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kaufman D. G., Baker M. S., Smith J. M., Henderson W. R., Harris C. C., Sporn M. B., Saffiotti U. RNA metabolism in tracheal epithelium: alteration in hamsters deficient in vitamin A. Science. 1972 Sep 22;177(4054):1105–1108. doi: 10.1126/science.177.4054.1105. [DOI] [PubMed] [Google Scholar]
  25. Loewenstein W. R. Permeability of membrane junctions. Ann N Y Acad Sci. 1966 Jul 14;137(2):441–472. doi: 10.1111/j.1749-6632.1966.tb50175.x. [DOI] [PubMed] [Google Scholar]
  26. Matoltsy A. G. Keratinization of the avian epidermis: an ultrastructural study of the newborn chick skin. J Ultrastruct Res. 1969 Dec;29(5):438–458. doi: 10.1016/s0022-5320(69)90065-3. [DOI] [PubMed] [Google Scholar]
  27. McMahon D. Chemical messengers in development: a hypothesis. Science. 1974 Sep 20;185(4156):1012–1021. doi: 10.1126/science.185.4156.1012. [DOI] [PubMed] [Google Scholar]
  28. McNutt N. S., Weinstein R. S. Membrane ultrastructure at mammalian intercellular junctions. Prog Biophys Mol Biol. 1973;26:45–101. doi: 10.1016/0079-6107(73)90017-5. [DOI] [PubMed] [Google Scholar]
  29. McNutt N. S., Weinstein R. S. The ultrastructure of the nexus. A correlated thin-section and freeze-cleave study. J Cell Biol. 1970 Dec;47(3):666–688. doi: 10.1083/jcb.47.3.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McNutt N. S., Weinstein R. S. The ultrastructure of the nexus. A correlated thin-section and freeze-cleave study. J Cell Biol. 1970 Dec;47(3):666–688. doi: 10.1083/jcb.47.3.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Montesano R., Friend D. S., Perrelet A., Orci L. In vivo assembly of tight junctions in fetal rat liver. J Cell Biol. 1975 Nov;67(2PT1):310–319. doi: 10.1083/jcb.67.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mottet N. K., Jensen H. M. The differentiation of chick embryonic skin. An electron microscopic study with a description of a peculiar epidermal cytoplasmic ultrastructure. Exp Cell Res. 1968 Sep;52(1):261–283. doi: 10.1016/0014-4827(68)90564-8. [DOI] [PubMed] [Google Scholar]
  33. Orci L., Amherdt M., Henquin J. C., Lambert A. E., Unger R. H., Renold A. E. Pronase effect on pancreatic beta cell secretion and morphology. Science. 1973 May 11;180(4086):647–649. doi: 10.1126/science.180.4086.647. [DOI] [PubMed] [Google Scholar]
  34. PELC S. R., FELL H. B. The effect of excess vitamin A on the uptake of labelled compounds by embryonic skin in organ culture. Exp Cell Res. 1960 Feb;19:99–113. doi: 10.1016/0014-4827(60)90041-0. [DOI] [PubMed] [Google Scholar]
  35. Parakkal P. F., Matoltsy A. G. An electron microscopic study of developing chick skin. J Ultrastruct Res. 1968 Jun;23(5):403–416. doi: 10.1016/s0022-5320(68)80106-6. [DOI] [PubMed] [Google Scholar]
  36. Revel J. P., Karnovsky M. J. Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol. 1967 Jun;33(3):C7–C12. doi: 10.1083/jcb.33.3.c7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Revel J. P., Yip P., Chang L. L. Cell junctions in the early chick embryo--a freeze etch study. Dev Biol. 1973 Dec;35(2):302–317. doi: 10.1016/0012-1606(73)90026-2. [DOI] [PubMed] [Google Scholar]
  38. Sani B. P., Hill D. L. Retinoic acid: a binding protein in chick embryo metatarsal skin. Biochem Biophys Res Commun. 1974 Dec 23;61(4):1276–1282. doi: 10.1016/s0006-291x(74)80422-5. [DOI] [PubMed] [Google Scholar]
  39. Schreiner E., Wolff K. Die Permeabilität des epidermalen Intercellularraumes für kleinmolekulares protein. Ergebnisse elektronenmikroskopisch-cytochemischer Untersuchungen mit Peroxidase als Markierungssubstanz. Arch Klin Exp Dermatol. 1969;235(1):78–88. [PubMed] [Google Scholar]
  40. Sheridan J. D. Dye movement and low-resistance junctions between reaggregated embryonic cells. Dev Biol. 1971 Dec;26(4):627–636. doi: 10.1016/0012-1606(71)90145-x. [DOI] [PubMed] [Google Scholar]
  41. Sheridan J. D. Dye movement and low-resistance junctions between reaggregated embryonic cells. Dev Biol. 1971 Dec;26(4):627–636. doi: 10.1016/0012-1606(71)90145-x. [DOI] [PubMed] [Google Scholar]
  42. Squier C. A. The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase. J Ultrastruct Res. 1973 Apr;43(1):160–177. doi: 10.1016/s0022-5320(73)90076-2. [DOI] [PubMed] [Google Scholar]
  43. Staehelin L. A. Structure and function of intercellular junctions. Int Rev Cytol. 1974;39:191–283. doi: 10.1016/s0074-7696(08)60940-7. [DOI] [PubMed] [Google Scholar]

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