Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Aug 15;90(16):7588–7592. doi: 10.1073/pnas.90.16.7588

The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation.

I Kola 1, S Brookes 1, A R Green 1, R Garber 1, M Tymms 1, T S Papas 1, A Seth 1
PMCID: PMC47187  PMID: 7689222

Abstract

The Ets family of genes encodes a class of transcription factors. Ets1 is predominantly expressed in the lymphoid organs of neonatal and adult mice, whereas Ets2 is expressed in every organ examined. In this study, we investigate the expression of Ets1 and Ets2 during murine embryonic development. Our data show that Ets1 expression increases in embryos after implantation and during organogenesis such that it is expressed in all the organs of day-15 embryos studied. In later fetal stages, Ets1 expression is predominant in the lymphoid tissues, brain, and organs that are undergoing branching morphogenesis (e.g., lung) but is dramatically reduced in other organs such as the stomach and intestine. In neonatal development, Ets1 is expressed only in the lymphoid organs and brain. In situ hybridization analysis demonstrates that expression of Ets1 occurs in mesenchymal cells of developing organs, in the nervous system, and in forming bone. Furthermore, expression of Ets1 is upregulated in P19 cells induced to differentiate into mesoderm-like cells. Ets2, on the other hand, is expressed in differentiated and undifferentiated P19 and F9 cells and in all organs of embryonic, neonatal, and adult mice studied. These data suggest that Ets1 plays an important role in mesodermal cells associated with morphogenetic processes such as organ formation and tissue modeling, whereas Ets2 plays a more fundamental role in cells.

Full text

PDF
7588

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amouyel P., Gégonne A., Delacourte A., Défossez A., Stéhelin D. Expression of ETS proto-oncogenes in astrocytes in human cortex. Brain Res. 1988 Apr 26;447(1):149–153. doi: 10.1016/0006-8993(88)90976-6. [DOI] [PubMed] [Google Scholar]
  2. Bhat N. K., Komschlies K. L., Fujiwara S., Fisher R. J., Mathieson B. J., Gregorio T. A., Young H. A., Kasik J. W., Ozato K., Papas T. S. Expression of ets genes in mouse thymocyte subsets and T cells. J Immunol. 1989 Jan 15;142(2):672–678. [PubMed] [Google Scholar]
  3. Biggs J., Murphy E. V., Israel M. A. A human Id-like helix-loop-helix protein expressed during early development. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1512–1516. doi: 10.1073/pnas.89.4.1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boulukos K. E., Pognonec P., Sariban E., Bailly M., Lagrou C., Ghysdael J. Rapid and transient expression of Ets2 in mature macrophages following stimulation with cMGF, LPS, and PKC activators. Genes Dev. 1990 Mar;4(3):401–409. doi: 10.1101/gad.4.3.401. [DOI] [PubMed] [Google Scholar]
  5. Burtis K. C., Thummel C. S., Jones C. W., Karim F. D., Hogness D. S. The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ets-related proteins. Cell. 1990 Apr 6;61(1):85–99. doi: 10.1016/0092-8674(90)90217-3. [DOI] [PubMed] [Google Scholar]
  6. Chen J. M., Little C. D. Cellular events associated with lung branching morphogenesis including the deposition of collagen type IV. Dev Biol. 1987 Apr;120(2):311–321. doi: 10.1016/0012-1606(87)90234-x. [DOI] [PubMed] [Google Scholar]
  7. Chen Z. Q., Burdett L. A., Seth A. K., Lautenberger J. A., Papas T. S. Requirement of ets-2 expression for Xenopus oocyte maturation. Science. 1990 Dec 7;250(4986):1416–1418. doi: 10.1126/science.2255913. [DOI] [PubMed] [Google Scholar]
  8. 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. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Dressler G. R., Douglass E. C. Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1179–1183. doi: 10.1073/pnas.89.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gehring W. J. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. doi: 10.1126/science.2884726. [DOI] [PubMed] [Google Scholar]
  11. Green A. R., Salvaris E., Begley C. G. Erythroid expression of the 'helix-loop-helix' gene, SCL. Oncogene. 1991 Mar;6(3):475–479. [PubMed] [Google Scholar]
  12. Gunther C. V., Nye J. A., Bryner R. S., Graves B. J. Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus. Genes Dev. 1990 Apr;4(4):667–679. doi: 10.1101/gad.4.4.667. [DOI] [PubMed] [Google Scholar]
  13. Gutman A., Wasylyk B. The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J. 1990 Jul;9(7):2241–2246. doi: 10.1002/j.1460-2075.1990.tb07394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ho I. C., Bhat N. K., Gottschalk L. R., Lindsten T., Thompson C. B., Papas T. S., Leiden J. M. Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. Science. 1990 Nov 9;250(4982):814–818. doi: 10.1126/science.2237431. [DOI] [PubMed] [Google Scholar]
  15. Hoch M., Gerwin N., Taubert H., Jäckle H. Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. Science. 1992 Apr 3;256(5053):94–97. doi: 10.1126/science.1348871. [DOI] [PubMed] [Google Scholar]
  16. Levine M., Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988 Nov 18;55(4):537–540. doi: 10.1016/0092-8674(88)90209-7. [DOI] [PubMed] [Google Scholar]
  17. Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990 Apr;6(4):121–125. doi: 10.1016/0168-9525(90)90126-q. [DOI] [PubMed] [Google Scholar]
  18. Mutter G. L., Wolgemuth D. J. Distinct developmental patterns of c-mos protooncogene expression in female and male mouse germ cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5301–5305. doi: 10.1073/pnas.84.15.5301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. O'Hara B. F., Fisher S., Oster-Granite M. L., Gearhart J. D., Reeves R. H. Developmental expression of the amyloid precursor protein, growth-associated protein 43, and somatostatin in normal and trisomy 16 mice. Brain Res Dev Brain Res. 1989 Oct 1;49(2):300–304. doi: 10.1016/0165-3806(89)90031-x. [DOI] [PubMed] [Google Scholar]
  20. Pribyl L. J., Watson D. K., Schulz R. A., Papas T. S. D-elg, a member of the Drosophila ets gene family: sequence, expression and evolutionary comparison. Oncogene. 1991 Jul;6(7):1175–1183. [PubMed] [Google Scholar]
  21. Rao V. N., Reddy E. S. A divergent ets-related protein, elk-1, recognizes similar c-ets-1 proto-oncogene target sequences and acts as a transcriptional activator. Oncogene. 1992 Jan;7(1):65–70. [PubMed] [Google Scholar]
  22. Roguska M. A., Gudas L. J. An increase in prolyl-4-hydroxylase activity occurs during the retinoic acid-induced differentiation of mouse teratocarcinoma stem cell lines F9 and P19. J Biol Chem. 1985 Nov 15;260(26):13893–13896. [PubMed] [Google Scholar]
  23. Sacchi N., Wendtner C. M., Thiele C. J. Single-cell detection of ets-1 transcripts in human neuroectodermal cells. Oncogene. 1991 Nov;6(11):2149–2154. [PubMed] [Google Scholar]
  24. Schöler H. R. Octamania: the POU factors in murine development. Trends Genet. 1991 Oct;7(10):323–329. doi: 10.1016/0168-9525(91)90422-m. [DOI] [PubMed] [Google Scholar]
  25. Seth A., Papas T. S. The c-ets-1 proto-oncogene has oncogenic activity and is positively autoregulated. Oncogene. 1990 Dec;5(12):1761–1767. [PubMed] [Google Scholar]
  26. Seth A., Watson D. K., Blair D. G., Papas T. S. c-ets-2 protooncogene has mitogenic and oncogenic activity. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7833–7837. doi: 10.1073/pnas.86.20.7833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thompson C. B., Wang C. Y., Ho I. C., Bohjanen P. R., Petryniak B., June C. H., Miesfeldt S., Zhang L., Nabel G. J., Karpinski B. cis-acting sequences required for inducible interleukin-2 enhancer function bind a novel Ets-related protein, Elf-1. Mol Cell Biol. 1992 Mar;12(3):1043–1053. doi: 10.1128/mcb.12.3.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Urness L. D., Thummel C. S. Molecular interactions within the ecdysone regulatory hierarchy: DNA binding properties of the Drosophila ecdysone-inducible E74A protein. Cell. 1990 Oct 5;63(1):47–61. doi: 10.1016/0092-8674(90)90287-o. [DOI] [PubMed] [Google Scholar]
  29. Vandenbunder B., Pardanaud L., Jaffredo T., Mirabel M. A., Stehelin D. Complementary patterns of expression of c-ets 1, c-myb and c-myc in the blood-forming system of the chick embryo. Development. 1989 Oct;107(2):265–274. doi: 10.1242/dev.107.2.265. [DOI] [PubMed] [Google Scholar]
  30. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  31. Wasylyk B., Wasylyk C., Flores P., Begue A., Leprince D., Stehelin D. The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. Nature. 1990 Jul 12;346(6280):191–193. doi: 10.1038/346191a0. [DOI] [PubMed] [Google Scholar]
  32. Wasylyk C., Gutman A., Nicholson R., Wasylyk B. The c-Ets oncoprotein activates the stromelysin promoter through the same elements as several non-nuclear oncoproteins. EMBO J. 1991 May;10(5):1127–1134. doi: 10.1002/j.1460-2075.1991.tb08053.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Watson D. K., McWilliams M. J., Lapis P., Lautenberger J. A., Schweinfest C. W., Papas T. S. Mammalian ets-1 and ets-2 genes encode highly conserved proteins. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7862–7866. doi: 10.1073/pnas.85.21.7862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wernert N., Raes M. B., Lassalle P., Dehouck M. P., Gosselin B., Vandenbunder B., Stehelin D. c-ets1 proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans. Am J Pathol. 1992 Jan;140(1):119–127. [PMC free article] [PubMed] [Google Scholar]
  35. Xin J. H., Cowie A., Lachance P., Hassell J. A. Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. Genes Dev. 1992 Mar;6(3):481–496. doi: 10.1101/gad.6.3.481. [DOI] [PubMed] [Google Scholar]
  36. de Haan J. B., Newman J. D., Kola I. Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. Brain Res Mol Brain Res. 1992 Apr;13(3):179–187. doi: 10.1016/0169-328x(92)90025-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES