• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 15, 1991; 88(4): 1516–1520.

Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3.


During early cardiac development, the progenitor cells of the heart valves and membranous septa undergo an epithelial-mesenchymal transformation. Previous studies have shown that this transformation depends on the activity of a transforming growth factor beta (TGF beta) molecule produced by the heart. In the present study, we have used modified antisense oligodeoxynucleotides generated to nonconserved regions of TGF beta 1, -2, -3, and -4 to examine the possible roles of these members in this transformation. A phosphoramidate-modified oligonucleotide complementary to TGF beta 3 mRNA was capable of inhibiting normal epithelial-mesenchymal transformation by 80%. Unmodified oligonucleotides to TGF beta 3, modified oligonucleotides to TGF beta 1, -2, and -4, and two modified control oligonucleotides were unable to inhibit the transformation. These data demonstrate that a specific member of the TGF beta family, TGF beta 3, is essential for the epithelial-mesenchymal cell transformation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Markwald RR, Fitzharris TP, Manasek FJ. Structural development of endocardial cushions. Am J Anat. 1977 Jan;148(1):85–119. [PubMed]
  • Runyan RB, Markwald RR. Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue. Dev Biol. 1983 Jan;95(1):108–114. [PubMed]
  • Markwald RR, Fitzharris TP, Bank H, Bernanke DH. Structural analyses on the matrical organization of glycosaminoglycans in developing endocardial cushions. Dev Biol. 1978 Feb;62(2):292–316. [PubMed]
  • Potts JD, Runyan RB. Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev Biol. 1989 Aug;134(2):392–401. [PubMed]
  • Runyan RB, Potts JD, Sharma RV, Loeber CP, Chiang JJ, Bhalla RC. Signal transduction of a tissue interaction during embryonic heart development. Cell Regul. 1990 Feb;1(3):301–313. [PMC free article] [PubMed]
  • Lehnert SA, Akhurst RJ. Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Development. 1988 Oct;104(2):263–273. [PubMed]
  • Akhurst RJ, Lehnert SA, Faissner A, Duffie E. TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis. Development. 1990 Apr;108(4):645–656. [PubMed]
  • Walder J. Antisense DNA and RNA: progress and prospects. Genes Dev. 1988 May;2(5):502–504. [PubMed]
  • Toulmé JJ, Hélène C. Antimessenger oligodeoxyribonucleotides: an alternative to antisense RNA for artificial regulation of gene expression--a review. Gene. 1988 Dec 10;72(1-2):51–58. [PubMed]
  • Dagle JM, Walder JA, Weeks DL. Targeted degradation of mRNA in Xenopus oocytes and embryos directed by modified oligonucleotides: studies of An2 and cyclin in embryogenesis. Nucleic Acids Res. 1990 Aug 25;18(16):4751–4757. [PMC free article] [PubMed]
  • Froehler BC, Ng PG, Matteucci MD. Synthesis of DNA via deoxynucleoside H-phosphonate intermediates. Nucleic Acids Res. 1986 Jul 11;14(13):5399–5407. [PMC free article] [PubMed]
  • Mjaatvedt CH, Lepera RC, Markwald RR. Myocardial specificity for initiating endothelial-mesenchymal cell transition in embryonic chick heart correlates with a particulate distribution of fibronectin. Dev Biol. 1987 Jan;119(1):59–67. [PubMed]
  • Jakowlew SB, Dillard PJ, Kondaiah P, Sporn MB, Roberts AB. Complementary deoxyribonucleic acid cloning of a novel transforming growth factor-beta messenger ribonucleic acid from chick embryo chondrocytes. Mol Endocrinol. 1988 Aug;2(8):747–755. [PubMed]
  • Krieg PA, Melton DA. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Krug EL, Runyan RB, Markwald RR. Protein extracts from early embryonic hearts initiate cardiac endothelial cytodifferentiation. Dev Biol. 1985 Dec;112(2):414–426. [PubMed]
  • Markwald RR, Funderburg FM. Use of 6-diazo-5-oxo-L-norleucine to study interaction between myocardial glycoconjugate secretion and endothelial activation in the early embryonic chick heart. Dev Biol. 1983 Oct;99(2):395–407. [PubMed]
  • Lyons KM, Pelton RW, Hogan BL. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development. 1990 Aug;109(4):833–844. [PubMed]
  • Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB, Sporn MB. Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice. J Cell Biol. 1989 Feb;108(2):661–669. [PMC free article] [PubMed]
  • Heine U, Munoz EF, Flanders KC, Ellingsworth LR, Lam HY, Thompson NL, Roberts AB, Sporn MB. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. [PMC free article] [PubMed]
  • Flanders KC, Thompson NL, Cissel DS, Van Obberghen-Schilling E, Baker CC, Kass ME, Ellingsworth LR, Roberts AB, Sporn MB. Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. J Cell Biol. 1989 Feb;108(2):653–660. [PMC free article] [PubMed]
  • Mjaatvedt CH, Markwald RR. Induction of an epithelial-mesenchymal transition by an in vivo adheron-like complex. Dev Biol. 1989 Nov;136(1):118–128. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...