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. 1990 Mar 1;110(3):753–765. doi: 10.1083/jcb.110.3.753

Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues

PMCID: PMC2116039  PMID: 1689733

Abstract

Immunohistochemical methods were used to study the distribution of basic FGF in the 18-d rat fetus. The results reveal a pattern of widespread yet specific staining that is consistent with the wide distribution of basic FGF. Immunoreactive basic FGF is associated with mesenchymal structures, mesoderm- and neuroectoderm-derived cells, and their extracellular matrices. As an example, skeletal and smooth muscle cells are strongly positive. The basement membrane underlying the epithelia always contain basic FGF. In some tissues (i.e., cartilage and bone) the intensity of immunostaining is dependent on the stage of cell differentiation. Although the staining of tissues is primarily associated with the extracellular matrix, there is significant intracellular staining in various cell types. This is particularly evident in the endocrine cells of the adrenal cortex, testis, and ovary. The histochemical findings reported here support the notion that basic FGF has the characteristics required to mediate many of the effects of the mesenchyme on cell growth and differentiation. The significance of these findings in understanding the role of basic FGF in regulating cell proliferation and differentiation is discussed.

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Selected References

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  1. Abraham J. A., Mergia A., Whang J. L., Tumolo A., Friedman J., Hjerrild K. A., Gospodarowicz D., Fiddes J. C. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. doi: 10.1126/science.2425435. [DOI] [PubMed] [Google Scholar]
  2. Abraham J. A., Whang J. L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J. C. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528. doi: 10.1002/j.1460-2075.1986.tb04530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson K. J., Dam D., Lee S., Cotman C. W. Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo. Nature. 1988 Mar 24;332(6162):360–361. doi: 10.1038/332360a0. [DOI] [PubMed] [Google Scholar]
  4. Baird A., Esch F., Mormède P., Ueno N., Ling N., Böhlen P., Ying S. Y., Wehrenberg W. B., Guillemin R. Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues. Recent Prog Horm Res. 1986;42:143–205. doi: 10.1016/b978-0-12-571142-5.50008-2. [DOI] [PubMed] [Google Scholar]
  5. Baird A., Ling N. Fibroblast growth factors are present in the extracellular matrix produced by endothelial cells in vitro: implications for a role of heparinase-like enzymes in the neovascular response. Biochem Biophys Res Commun. 1987 Jan 30;142(2):428–435. doi: 10.1016/0006-291x(87)90292-0. [DOI] [PubMed] [Google Scholar]
  6. Baird A., Ueno N., Esch F., Ling N. Distribution of fibroblast growth factors (FGFs) in tissues and structure-function studies with synthetic fragments of basic FGF. J Cell Physiol Suppl. 1987;Suppl 5:101–106. doi: 10.1002/jcp.1041330419. [DOI] [PubMed] [Google Scholar]
  7. Barr P. J., Cousens L. S., Lee-Ng C. T., Medina-Selby A., Masiarz F. R., Hallewell R. A., Chamberlain S. H., Bradley J. D., Lee D., Steimer K. S. Expression and processing of biologically active fibroblast growth factors in the yeast Saccharomyces cerevisiae. J Biol Chem. 1988 Nov 5;263(31):16471–16478. [PubMed] [Google Scholar]
  8. Böhlen P., Esch F., Baird A., Jones K. L., Gospodarowicz D. Human brain fibroblast growth factor. Isolation and partial chemical characterization. FEBS Lett. 1985 Jun 3;185(1):177–181. doi: 10.1016/0014-5793(85)80765-1. [DOI] [PubMed] [Google Scholar]
  9. Clegg C. H., Linkhart T. A., Olwin B. B., Hauschka S. D. Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor. J Cell Biol. 1987 Aug;105(2):949–956. doi: 10.1083/jcb.105.2.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Danielsen N., Pettmann B., Vahlsing H. L., Manthorpe M., Varon S. Fibroblast growth factor effects on peripheral nerve regeneration in a silicone chamber model. J Neurosci Res. 1988 Jul;20(3):320–330. doi: 10.1002/jnr.490200306. [DOI] [PubMed] [Google Scholar]
  11. DiMario J., Buffinger N., Yamada S., Strohman R. C. Fibroblast growth factor in the extracellular matrix of dystrophic (mdx) mouse muscle. Science. 1989 May 12;244(4905):688–690. doi: 10.1126/science.2717945. [DOI] [PubMed] [Google Scholar]
  12. Esch F., Baird A., Ling N., Ueno N., Hill F., Denoroy L., Klepper R., Gospodarowicz D., Böhlen P., Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. doi: 10.1073/pnas.82.19.6507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fauser B. C., Baird A., Hsueh A. J. Fibroblast growth factor inhibits luteinizing hormone-stimulated androgen production by cultured rat testicular cells. Endocrinology. 1988 Dec;123(6):2935–2941. doi: 10.1210/endo-123-6-2935. [DOI] [PubMed] [Google Scholar]
  14. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  15. Folkman J., Klagsbrun M., Sasse J., Wadzinski M., Ingber D., Vlodavsky I. A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. Am J Pathol. 1988 Feb;130(2):393–400. [PMC free article] [PubMed] [Google Scholar]
  16. Globus R. K., Patterson-Buckendahl P., Gospodarowicz D. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta. Endocrinology. 1988 Jul;123(1):98–105. doi: 10.1210/endo-123-1-98. [DOI] [PubMed] [Google Scholar]
  17. Gospodarowicz D., Cheng J., Lui G. M., Baird A., Esch F., Bohlen P. Corpus luteum angiogenic factor is related to fibroblast growth factor. Endocrinology. 1985 Dec;117(6):2383–2391. doi: 10.1210/endo-117-6-2383. [DOI] [PubMed] [Google Scholar]
  18. Gospodarowicz D., Cheng J., Lui G. M., Fujii D. K., Baird A., Böhlen P. Fibroblast growth factor in the human placenta. Biochem Biophys Res Commun. 1985 Apr 30;128(2):554–562. doi: 10.1016/0006-291x(85)90082-8. [DOI] [PubMed] [Google Scholar]
  19. Gospodarowicz D., Ferrara N., Schweigerer L., Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev. 1987 May;8(2):95–114. doi: 10.1210/edrv-8-2-95. [DOI] [PubMed] [Google Scholar]
  20. Gospodarowicz D., Ill C. R., Hornsby P. J., Gill G. N. Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor. Endocrinology. 1977 Apr;100(4):1080–1089. doi: 10.1210/endo-100-4-1080. [DOI] [PubMed] [Google Scholar]
  21. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor. Mol Cell Endocrinol. 1986 Aug;46(3):187–204. doi: 10.1016/0303-7207(86)90001-8. [DOI] [PubMed] [Google Scholar]
  22. Hauschka P. V., Mavrakos A. E., Iafrati M. D., Doleman S. E., Klagsbrun M. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem. 1986 Sep 25;261(27):12665–12674. [PubMed] [Google Scholar]
  23. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hornsby P. J., Gill G. N. Hormonal control of adrenocortical cell proliferation. Desensitization to ACTH and interaction between ACTH and fibroblast growth factor in bovine adrenocortical cell cultures. J Clin Invest. 1977 Aug;60(2):342–352. doi: 10.1172/JCI108782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Joseph-Silverstein J., Consigli S. A., Lyser K. M., Ver Pault C. Basic fibroblast growth factor in the chick embryo: immunolocalization to striated muscle cells and their precursors. J Cell Biol. 1989 Jun;108(6):2459–2466. doi: 10.1083/jcb.108.6.2459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kimelman D., Abraham J. A., Haaparanta T., Palisi T. M., Kirschner M. W. The presence of fibroblast growth factor in the frog egg: its role as a natural mesoderm inducer. Science. 1988 Nov 18;242(4881):1053–1056. doi: 10.1126/science.3194757. [DOI] [PubMed] [Google Scholar]
  27. Kimelman D., Kirschner M. Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell. 1987 Dec 4;51(5):869–877. doi: 10.1016/0092-8674(87)90110-3. [DOI] [PubMed] [Google Scholar]
  28. Liu L. M., Nicoll C. S. Evidence for a role of basic fibroblast growth factor in rat embryonic growth and differentiation. Endocrinology. 1988 Oct;123(4):2027–2031. doi: 10.1210/endo-123-4-2027. [DOI] [PubMed] [Google Scholar]
  29. Mascarelli F., Raulais D., Counis M. F., Courtois Y. Characterization of acidic and basic fibroblast growth factors in brain, retina and vitreous chick embryo. Biochem Biophys Res Commun. 1987 Jul 31;146(2):478–486. doi: 10.1016/0006-291x(87)90554-7. [DOI] [PubMed] [Google Scholar]
  30. Mergia A., Eddy R., Abraham J. A., Fiddes J. C., Shows T. B. The genes for basic and acidic fibroblast growth factors are on different human chromosomes. Biochem Biophys Res Commun. 1986 Jul 31;138(2):644–651. doi: 10.1016/s0006-291x(86)80545-9. [DOI] [PubMed] [Google Scholar]
  31. Morrison R. S., Sharma A., de Vellis J., Bradshaw R. A. Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7537–7541. doi: 10.1073/pnas.83.19.7537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Otto D., Unsicker K., Grothe C. Pharmacological effects of nerve growth factor and fibroblast growth factor applied to the transectioned sciatic nerve on neuron death in adult rat dorsal root ganglia. Neurosci Lett. 1987 Dec 16;83(1-2):156–160. doi: 10.1016/0304-3940(87)90233-3. [DOI] [PubMed] [Google Scholar]
  33. Petroutsos G., Courty J., Guimaraes R., Pouliquen Y., Barritault D., Plouët J., Courtois Y. Comparison of the effects of EGF, pFGF and EDGF on corneal epithelium wound healing. Curr Eye Res. 1984 Apr;3(4):593–598. doi: 10.3109/02713688409003059. [DOI] [PubMed] [Google Scholar]
  34. Risau W. Developing brain produces an angiogenesis factor. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3855–3859. doi: 10.1073/pnas.83.11.3855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Risau W., Ekblom P. Production of a heparin-binding angiogenesis factor by the embryonic kidney. J Cell Biol. 1986 Sep;103(3):1101–1107. doi: 10.1083/jcb.103.3.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Risau W., Gautschi-Sova P., Böhlen P. Endothelial cell growth factors in embryonic and adult chick brain are related to human acidic fibroblast growth factor. EMBO J. 1988 Apr;7(4):959–962. doi: 10.1002/j.1460-2075.1988.tb02901.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schubert D., Ling N., Baird A. Multiple influences of a heparin-binding growth factor on neuronal development. J Cell Biol. 1987 Mar;104(3):635–643. doi: 10.1083/jcb.104.3.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schweigerer L. Basic fibroblast growth factor as a wound healing hormone. Trends Pharmacol Sci. 1988 Dec;9(12):427–428. doi: 10.1016/0165-6147(88)90125-3. [DOI] [PubMed] [Google Scholar]
  39. Seed J., Olwin B. B., Hauschka S. D. Fibroblast growth factor levels in the whole embryo and limb bud during chick development. Dev Biol. 1988 Jul;128(1):50–57. doi: 10.1016/0012-1606(88)90265-5. [DOI] [PubMed] [Google Scholar]
  40. Shimasaki S., Emoto N., Koba A., Mercado M., Shibata F., Cooksey K., Baird A., Ling N. Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA. Biochem Biophys Res Commun. 1988 Nov 30;157(1):256–263. doi: 10.1016/s0006-291x(88)80041-x. [DOI] [PubMed] [Google Scholar]
  41. Simpson R. J., Moritz R. L., Lloyd C. J., Fabri L. J., Nice E. C., Rubira M. R., Burgess A. W. Primary structure of ovine pituitary basic fibroblast growth factor. FEBS Lett. 1987 Nov 16;224(1):128–132. doi: 10.1016/0014-5793(87)80435-0. [DOI] [PubMed] [Google Scholar]
  42. Slack J. M., Darlington B. G., Heath J. K., Godsave S. F. Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature. 1987 Mar 12;326(6109):197–200. doi: 10.1038/326197a0. [DOI] [PubMed] [Google Scholar]
  43. Sommer A., Brewer M. T., Thompson R. C., Moscatelli D., Presta M., Rifkin D. B. A form of human basic fibroblast growth factor with an extended amino terminus. Biochem Biophys Res Commun. 1987 Apr 29;144(2):543–550. doi: 10.1016/s0006-291x(87)80001-3. [DOI] [PubMed] [Google Scholar]
  44. Unsicker K., Reichert-Preibsch H., Schmidt R., Pettmann B., Labourdette G., Sensenbrenner M. Astroglial and fibroblast growth factors have neurotrophic functions for cultured peripheral and central nervous system neurons. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5459–5463. doi: 10.1073/pnas.84.15.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Walicke P., Cowan W. M., Ueno N., Baird A., Guillemin R. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci U S A. 1986 May;83(9):3012–3016. doi: 10.1073/pnas.83.9.3012. [DOI] [PMC free article] [PubMed] [Google Scholar]

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