Extracellular Matrix Involvement in Epithelial Branching Morphogenesis

  • Brian S. Spooner
  • Holly A. Thompson-Pletscher
  • Brad Stokes
  • Kenneth E. Bassett
Part of the Developmental Biology book series (DEBO, volume 3)


Branching morphogenesis is a major developmental process used by a large array of embryonic organs. Examples of organs whose development involves branching morphogenesis include submandibular, sublingual, and parotid sali vary glands, mammary glands, lungs, pancreas, and kidneys. In each case, an epithelium undergoes repeated branching activity, in concert with mitotic growth, that results in the formation of an organ-specific pattern of clefts or branch points and the generation of large amounts of epithelial surface area for the available amount of organ space. The advantage would appear to be that epithelial surface area for such functions as secretory activity and gas exchange is maximized, resulting in highly efficient compact organs.


Basal Lamina Anionic Site Proteoglycan Synthesis Lamina Densa LACA Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alescio, T., 1973, Effect of a proline analog, azetidine-2-carboxylic acid, on the morphogenesis in vitro of mouse embryonic lung, J. EmbryoJ. Exp. Morphol. 29:493–514.Google Scholar
  2. Alescio, T., and Cassini, A., 1962, Induction in vitro of tracheal buds by pulmonary mesenchyme grafted on tracheal epithelium, J. Exp. Zool. 150:83–94.PubMedCrossRefGoogle Scholar
  3. Ash, J. F., Spooner, B. S., and Wessells, N. K. ,1973, Effects of papaverine and calcium-free medium on salivary gland morphogenesis, Dev. Biol. 33:463–469.PubMedCrossRefGoogle Scholar
  4. Aydelotte, M., and Kochhar, D., 1975, Influence of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog, on cartilagenous differentiation in mouse limb buds in vitro, Differentiation 4:73–80.PubMedCrossRefGoogle Scholar
  5. Banerjee, S. D., Cohn, R. H., and Bernfield, M. R., 1977, Basal lamina of embryonic salivary epithelia: Production by the epithelium and role in maintaining lobular morphology, J. Cell Biol. 73:445–463.PubMedCrossRefGoogle Scholar
  6. Bates, C.J., Adams, W. R., and Handschumacher, R. E. ,1966, Control of formation of uridine diphospho-N-acetyl-hexosamine and glycoprotein synthesis in rat liver, J. Biol. Chem. 241:1705–1712.PubMedGoogle Scholar
  7. Bernfield, M. R., 1970, Collagen synthesis during epitheliomesenchymal interactions, Dev. Biol. 22:213–231.PubMedCrossRefGoogle Scholar
  8. Bernfield, M. R.,1981, Organization and remodeling of the extracellular matrix in morphogenesis, in: Morphogenesis and Pattern Formation: Implications for Normal and Abnormal Develop ment (L. L. Brinkley, B. M. Carlson, and T. G. Connelly, eds.), pp. 139–162, Raven Press, New York.Google Scholar
  9. Bernfield, M. R., and Banerjee, S. D., 1972, Acid mucopolysaccharide (glycosaminoglycan) at the epithelial-mesenchymal interface of mouse embryo salivary glands, J. Cell Biol. 52:664–673.PubMedCrossRefGoogle Scholar
  10. Bernfield, M. R., and Banerjee, S. D., 1982, The turnover of basal lamina glycosaminoglycan correlates with epithelial morphogenesis, Dev. Biol. 90:291–305.PubMedCrossRefGoogle Scholar
  11. Bernfield, M. R., Banerjee, S. D., and Cohn, R. H., 1972, Dependence of salivary epithelial morphology and branching morphogenesis upon acid mucopolysaccharide-protein (proteoglycan) at the epithelial surface, J. Cell Biol. 52:674–689.PubMedCrossRefGoogle Scholar
  12. Bernfield, M. R., Cohn, R. H., and Banerjee, S. D., 1973, Glycosaminoglycans and epithelial organ formation, Am. Zool. 13:1067–1083.Google Scholar
  13. Bornstein, P. ,and Traub, W., 1979, The chemistry and biology of collagen, in: The Proteins ,Vol. IV (H. Neurath and R. L. Hall, eds.), pp. 411–432, Academic Press, New York.Google Scholar
  14. Cohn, R. H., Banerjee, S. D., and Bernfield, M. R., 1977, Basal lamina of embryonic salivary epithelia. Nature of glycosaminoglycan and organization of extracellular materials, J. Cell Biol. 73:464–478.PubMedCrossRefGoogle Scholar
  15. Coulombre, J., and Coulombre, A. ,1975, Corneal development. V. Treatment of five-day-old embryos of domestic fowl with 6-diazo-5-oxo-L-norleucine (DON), Dev. Biol. 45:291–303.PubMedCrossRefGoogle Scholar
  16. Crouch, E., and Bornstein, P. ,1979, Characterization of a type IV procollagen synthesized by human amniotic fluid cells in culture, J. Biol. Chem. 254:4197–4204.PubMedGoogle Scholar
  17. David, G.,and Bernfield, M. R., 1979, Collagen reduces glycosaminoglycan degradation by cultured mammary epithelial cells: A possible mechanism for basal lamina formation, Proc. Nstl.Acad. Sci. USA 76:786–790.CrossRefGoogle Scholar
  18. Duksin, D., Seiberg, M. ,and Mahoney, W. C.,1982, Inhibition of protein glycosylation and selective toxicity toward virally transformed fibroblasts caused by B3-tunicamycin, Eur. J. Biochem. 129:77–80.PubMedCrossRefGoogle Scholar
  19. Ekblom, P., Lash, J. W., Lehtonen, E., Nordling, S. ,and Saxén, L., 1979, Inhibition of morphogenetic cell interactions by 6-diazo-5-oxo-L-norleucine (DON), Exp. Cell Res. 121:121–126.PubMedCrossRefGoogle Scholar
  20. Essner, E., and Pino, R. M., 1982, Distribution of anionic sites in Bruch’s membrane of the rabbit eye, Eur. J. Cell Biol. 27:251–255.PubMedGoogle Scholar
  21. Farquhar, M. G., 1978, Recovery of surface membrane in anterior pituitary cells. Variations in traffic detected with anionic and cationic ferritin, J. Cell Biol. 77:R35–R42.PubMedCrossRefGoogle Scholar
  22. Fukunaga, Y., Sobue, M. ,Suzuki, N., Kushida, H., Suzuki, S., and Suzuki, S., 1975, Synthesis of fluorogenic mucopolysaccharide by chondrocytes in cell culture with 4-methylumbelliferyl-ß-xyloside, Biochim. Biophys. Acta 381:443–447.PubMedCrossRefGoogle Scholar
  23. Galligani, L., Hopwood, J. ,Schwartz, N. B., and Dorfman, A., 1975, Stimulation of synthesis of free chondroitin sulfate chains by ß-D-xylosides in cultured cells, J. Biol. Chem. 250:5400–5406.PubMedGoogle Scholar
  24. Ghosh, S., Blumenthal, H. J. ,Davidson, E., and Roseman, S., 1960, Glucosamine metabolism. V. Enzymatic synthesis of glucosamine-6-phosphate, J. Biol. Chem. 235:1265–1273.PubMedGoogle Scholar
  25. Grant, M. M., Cutts, N. R., and Brody, J. S. ,1983, Alterations in lung basement membrane during fetal growth and type 2 cell development, Dev. Biol. 97:173–183.PubMedCrossRefGoogle Scholar
  26. Greene, R. M. ,and Pratt, R. M. ,1977, Inhibition by diazo-oxo-norleucine (DON) of at palatal glycoprotein synthesis and epithelial cell adhesion in vitro, Exp. Cell Bes. 105:27–37.CrossRefGoogle Scholar
  27. Grobstein, C., 1953, Epithelio-mesenchymal specificity in the morphogenesis of mouse submandibular rudiments in vitro, J. Exp. Zool. 124:383–404.CrossRefGoogle Scholar
  28. Grobstein, C., 1967, Mechanism of organogenetic tissue interaction, Nstl. Cancer. Inst. Monogr. 26:279–299.Google Scholar
  29. Grobstein, C., and Cohen, J., 1965, Collagenase: Effect on the morphogenesis of embryonic salivary epithelium in vitro, Science 150:626–628.PubMedCrossRefGoogle Scholar
  30. Hall, H. G., Farson, D. A., and Bissell, M. J., 1982, Lumen formation by epithelial cell lines in response to collagen overlay: A morphogenetic model in culture, Proc. Nstl. Acad. Sci. USA 79:4672–4676.CrossRefGoogle Scholar
  31. Hart, G. W., 1982, The role of asparagine-linked oligosaccharides in cellular recognition by thymic lymphocytes, J. Biol. Chem. 257:151–158.PubMedGoogle Scholar
  32. Hart, G. W., and Lennarz, W. J., 1978, Effects of tunicamycin on the biosynthesis of glycosaminoglycans by embryonic chick cornea, J. Biol. Chem. 253:5795–5801.PubMedGoogle Scholar
  33. Hill, D. L., and Bennett, L. L., Jr., 1969, Purification and properties of 5-phosphoribosyl pyrophosphate aminotransferase from adenocarcinoma 755 cells, Biochemistry 8:122–130.PubMedCrossRefGoogle Scholar
  34. Hurmerinta, K., and Thesleff, I., 1982, Diazo-oxo-norleucine (DON)-induced alterations in the extracellular matrix of the mouse tooth germ, Cell Diff. 11:107–113.CrossRefGoogle Scholar
  35. Hurmerinta, K., Thesleff, I., and Saxén, L., 1979, Inhibition of tooth germ differentiation in vitro by diazo-oxo-norleucine (DON), J. EmbryoJ. Exp. Morphol. 50:99–109.Google Scholar
  36. Ishii, K., and Green, H., 1973, Lethality of adenosine for cultured mammalian cells by interference with pyrimidine biosynthesis, J. Cell Sci. 13:429–439.PubMedGoogle Scholar
  37. Kallman, F., and Grobstein, C., 1965, Source of collagen at epitheliomesenchymal interfaces during inductive interaction, Dev. Biol. 11:169–183.PubMedCrossRefGoogle Scholar
  38. Kallman, F., and Grobstein, C., 1966, Localization of glucosamine-incorporating materials at epihelial surfaces during salivary epitheliomesenchymal interaction in vitro, Dev. Biol. 14:52–67.PubMedCrossRefGoogle Scholar
  39. Kim, J. J., and Conrad, H. E., 1974, Effect of D-glucosamine concentration on the kinetics of mucopolysaccharide biosynthesis in cultured chick embryo vertebral cartilage, J. Biol. Chem. 249:3091–3097.PubMedGoogle Scholar
  40. Lane, J. M., Parkes, L. J., and Prockop, D. J., 1971, Effect of the proline analog azetidine-2-carboxylic acid on collagen synthesis in vivo. II. Morphological and physical properties of collagen containing the analog, Biochim. Biophys. Acta 236:528–541.PubMedGoogle Scholar
  41. Linsenmayer, T. F., and Kochhar, D. M., 1979, In vitro cartilage formation: Effects of 6-diazo-5-oxo-norleucine (DON) on glycosaminoglycan and collagen synthesis, Dev. Biol. 69:517–528.PubMedCrossRefGoogle Scholar
  42. Lohmander, S., Madsen, K., and Hinek, A., 1979, Secretion of proteoglycans by chondrocytes: Influence of colchicine, cytochalasin B, and ß-D-xyloside, Arch. Biochim. Biophys. 192:148–157.CrossRefGoogle Scholar
  43. Mahoney, W. C., and Duksin, D., 1979, Biological activities of the two major components of tunicamycin, J. Biol. Chem. 254:6572–6576.PubMedGoogle Scholar
  44. Meier, S., and Hay, E. D., 1974, Control of corneal differentiation by extracellular materials: Collagen as a promoter and stabilizer of epithelial stroma production, Dev. Biol. 38:249–270.PubMedCrossRefGoogle Scholar
  45. Pinnell, S. R., and Martin, G. R., 1968, The cross-linking of collagen and elastin: Enzymatic converion of lysine in peptide linkage to a-aminoadipic-5-semialdehyde by an extract of bone, Proc. Nstl.Acad. Sci. USA 61:708–716.CrossRefGoogle Scholar
  46. Pratt, R. M., and Greene, R. M., 1976, Inhibition of palatal epithelial cell death by altered protein synthesis, Dev. Biol. 54: 135–145.PubMedCrossRefGoogle Scholar
  47. Sakakura, T., Nishizuka, Y., and Dawe, C. J., 1976, Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland, Science 194:1439.PubMedCrossRefGoogle Scholar
  48. Schurer, J. W., Kalicharan, D., Hoedemaeker, J., and Molenaar, I., 1978, The use of polyethylneimine for demonstration of anionic sites in basement membranes and collagen fibrils, J. Histochem. Cytochem. 26:688–689.PubMedCrossRefGoogle Scholar
  49. Schwartz, N. B., 1977, Regulation of chondroitin sulfate synthesis: Effect of ß-xylosides on synthesis of chondroitin sulfate chains and core proteins, J. Biol. Chem. 252:6316–6321.PubMedGoogle Scholar
  50. Schwartz, N. B., Galligani, L., Ho, P. L., and Dorfman, A., 1974, Stimulation of synthesis of free chondroitin sulfate chains by ß-D-xylosides in cultured cells, Proc. Nstl. Acad. Sci. USA 71: 4047–4051.CrossRefGoogle Scholar
  51. Simionescu, M., Simionescu, N., and Palade, G. E., 1982, Preferential distribution of anionic sites on the basement membrane and the abluminal aspect of the endothelium in fenestrated capillaries, J. Cell Biol. 95:425–434.PubMedCrossRefGoogle Scholar
  52. Smith, R. L. ,and Bernfield, M. R., 1982, Mesenchyme cells degrade epithelial basal lamina pro teoglycan, Dev. Biol. 94:378–390.PubMedCrossRefGoogle Scholar
  53. Spooner, B. S., 1973, Microfilaments, cell shape changes, and morphogenesis of salivary epithelium, Am. Zool. 13: 1007–1022.Google Scholar
  54. Spooner, B. S., 1974, Morphogenesis of vertebrate organs, in: Concepts of Development (J. Lash and J. R. Whittaker, Eds.), pp. 213–240, Sinauer Associates, Stanford, Connecticut.Google Scholar
  55. Spooner, B. S., 1975, Microfilaments, microtubules, and extracellular materials in morphogenesis, BioScience 25:440–451.Google Scholar
  56. Spooner, B. S., and Conrad, G. W., 1975, The role of extracellular materials in cell movement. I. Inhibition of mucopolysaccharide synthesis does not stop ruffling membrane activity or cell movement, J. Cell Biol. 65:286–297.PubMedCrossRefGoogle Scholar
  57. Spooner, B. S., and Faubion, J. M., 1980, Collagen involvement in branching morphogenesis of embryonic lung and salivary gland, Dev. Biol. 77:84–102.PubMedCrossRefGoogle Scholar
  58. Spooner, B. S., and Wessells, N. K., 1970, Mammalian lung development: Interactions in primordium formation and bronchial morphogenesis, J. Exp. Zool. 175:445–454.PubMedCrossRefGoogle Scholar
  59. Spooner, B. S., and Wessells, N. K., 1972, An analysis of salivary gland morphogenesis: Role of cytoplasmic microfilaments and microtubules, Dev. Biol. 27:38–54.PubMedCrossRefGoogle Scholar
  60. Spooner, B. S. ,Ash, J. F., Wrenn, J. T., Frater, R. B., and Wessells, N. K., 1973, Heavy meromyosin binding to microfilaments involved in cell and morphogenetic movements, Tissue Cell 5:37–46.PubMedCrossRefGoogle Scholar
  61. Spooner, B. S. ,Cohen, H. I., and Faubion, J., 1977, Development of the embryonic mammalian pancreas: The relationship between morphogenesis and cytodifferentiation, Dev. Biol. 61:119–130.PubMedCrossRefGoogle Scholar
  62. Spooner, B. S., Ash, J. F., and Wessells, N. K., 1978, Actin in embryonic organ epithelia, Exp. Cell Bes. 114:381–387.CrossRefGoogle Scholar
  63. Spooner, B. S., Bassett, K., and Stokes, B., 1985, Sulfated glycosaminoglycan deposition and processing at the basal epithelial surface in branching and ß-D-xyloside-inhibited embryonic salivary glands; Dev. Biol. 109:177–183.PubMedCrossRefGoogle Scholar
  64. Switzer, B. R., and Summer, G. K. ,1973, Inhibition of collagen synthesis by dipyridyl in human skin fibroblasts in culture, In Vitro 9:160–166.PubMedCrossRefGoogle Scholar
  65. Taderera, J. V., 1967, Control of lung differentiation in vitro, Dev. Biol. 16:489–512.PubMedCrossRefGoogle Scholar
  66. Takeuchi, T., and Prockop, D. J. ,1969, Biosynthesis of abnormal collagens with amino acid analogs. I. Incorporation of L-azetidine-2-carboxylic acid and cis-4-fluoro-L-proline into proocollagen and collagen, Biochim. Biophys. Acta 175:142–155.PubMedGoogle Scholar
  67. Takeuchi, T., Rosenbloom, J., and Prockop, D. J., 1969, Biosynthesis of abnormal collagens with amino acid analogs. II. Inability of cartilage cells to extrude polypeptides containing lzetidine-2-carboxylic acid or cis-4-fIuoro-L-proline, Biochim. Biophys. Acta 175:156–64.PubMedGoogle Scholar
  68. Thompson, H. A., and Spooner, B. S., 1982, Inhibition of branching morphogenesis and alteration of glycosaminoglycan biosynthesis in salivary glands treated with ß-D-xyloside, Dev. Biol. 89:417–424.PubMedCrossRefGoogle Scholar
  69. Thompson, H. A., and Spooner, B. S. ,1983, Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: Effects of ß-D-xyloside, an inhibitor of branching morphogenesis, J. Cell Biol. 96:1443–1450.PubMedCrossRefGoogle Scholar
  70. Uitto, J. ,and Prockop, D.J., 1974, Incorporation of proline analogs into collagen polypeptides: Effects on the production of extracellular procollagen and on the stability of the triple-helical structure of the molecule, Biochim. Biophys. Acta 336:234–251.Google Scholar
  71. Uitto,J. ,Hoffman, H.-P., and Prockop, D. J. ,1976, Synthesis of elastin and procollagen by cells from embryonic aorta. Differences in the role of hydroxyproline and the effects of proline analogs on the secretion of the two proteins, Arch. Biochem. Biophys. 173:187–200.PubMedCrossRefGoogle Scholar
  72. Vaccaro, C. A., and Brody, J. S., 1981, Structural features of alveolar wall basement membrane in the adult rat lung, J. Cell Biol. 91:427–437.PubMedCrossRefGoogle Scholar
  73. Wessells, N. K., 1970, Mammalian lung development: Interactions in formation and morphogenesis of tracheal buds, J. Exp. Zool. 175,455–466.PubMedCrossRefGoogle Scholar
  74. Wessells, N. K., and Cohen, J. H., 1968, Effects of collagenase on developing epithelia in vitro: Lung, ureteric bud, and pancreas, Dev. Biol. 18:294–309.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Brian S. Spooner
    • 1
  • Holly A. Thompson-Pletscher
    • 2
  • Brad Stokes
    • 1
  • Kenneth E. Bassett
    • 1
  1. 1.Division of BiologyKansas State UniversityManhattanUSA
  2. 2.Department of ChemistryUniversity of MontanaMissoulaUSA

Personalised recommendations