Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. Oct 1, 1993; 123(1): 223–235.
PMCID: PMC2119804

Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development

Abstract

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine kinase. We report here the novel and distinct expression patterns of SF/HGF and its receptor during mouse development, which was determined by a combination of in situ hybridization and RNase protection experiments. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in distinct mesenchymal cells in close vicinity. In addition, transient SF/HGF and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple developmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern differentiation and morphogenesis of many epithelia, but the molecular nature of the signals has remained poorly understood. Therefore, the known biological activities of SF/HGF in vitro and the embryonal expression pattern reported here indicate that this mesenchymal factor can transmit morphogenetic signals in epithelial development and suggest a molecular mechanism for mesenchymal epithelial interactions.

Full Text

The Full Text of this article is available as a PDF (5.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Auffray C, Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. [PubMed]
  • Basler K, Hafen E. Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain. Cell. 1988 Jul 29;54(3):299–311. [PubMed]
  • Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981 Oct;26(2 Pt 2):167–180. [PubMed]
  • Birchmeier C, Birchmeier W. Molecular aspects of mesenchymal-epithelial interactions. Annu Rev Cell Biol. 1993;9:511–540. [PubMed]
  • Birchmeier C, Birnbaum D, Waitches G, Fasano O, Wigler M. Characterization of an activated human ros gene. Mol Cell Biol. 1986 Sep;6(9):3109–3116. [PMC free article] [PubMed]
  • Birchmeier C, Sharma S, Wigler M. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9270–9274. [PMC free article] [PubMed]
  • Birchmeier C, Sonnenberg E, Weidner KM, Walter B. Tyrosine kinase receptors in the control of epithelial growth and morphogenesis during development. Bioessays. 1993 Mar;15(3):185–190. [PubMed]
  • Blair DG, Cooper CS, Oskarsson MK, Eader LA, Vande Woude GF. New method for detecting cellular transforming genes. Science. 1982 Dec 10;218(4577):1122–1125. [PubMed]
  • Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802–804. [PubMed]
  • Chan AM, King HW, Deakin EA, Tempest PR, Hilkens J, Kroezen V, Edwards DR, Wills AJ, Brookes P, Cooper CS. Characterization of the mouse met proto-oncogene. Oncogene. 1988 Jun;2(6):593–599. [PubMed]
  • Dean M, Park M, Vande Woude GF. Characterization of the rearranged tpr-met oncogene breakpoint. Mol Cell Biol. 1987 Feb;7(2):921–924. [PMC free article] [PubMed]
  • Defrances MC, Wolf HK, Michalopoulos GK, Zarnegar R. The presence of hepatocyte growth factor in the developing rat. Development. 1992 Oct;116(2):387–395. [PubMed]
  • Di Renzo MF, Narsimhan RP, Olivero M, Bretti S, Giordano S, Medico E, Gaglia P, Zara P, Comoglio PM. Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. 1991 Nov;6(11):1997–2003. [PubMed]
  • Fell PE, Grobstein C. The influence of extra-epithelial factors on the growth of embryonic mouse pancreatic epithelium. Exp Cell Res. 1968 Oct;53(1):301–304. [PubMed]
  • Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. [PubMed]
  • Gherardi E. Growth factors and cell movement. Eur J Cancer. 1991;27(4):403–405. [PubMed]
  • Gherardi E, Gray J, Stoker M, Perryman M, Furlong R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5844–5848. [PMC free article] [PubMed]
  • Giordano S, Ponzetto C, Di Renzo MF, Cooper CS, Comoglio PM. Tyrosine kinase receptor indistinguishable from the c-met protein. Nature. 1989 May 11;339(6220):155–156. [PubMed]
  • Gonzatti-Haces M, Seth A, Park M, Copeland T, Oroszlan S, Vande Woude GF. Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1988 Jan;85(1):21–25. [PMC free article] [PubMed]
  • Grobstein C. Mechanisms of organogenetic tissue interaction. Natl Cancer Inst Monogr. 1967 Sep;26:279–299. [PubMed]
  • Grobstein C, Cohen J. Collagenase: effect on the morphogenesis of embryonic salivary epithelium in vitro. Science. 1965 Oct 29;150(3696):626–628. [PubMed]
  • Hampe A, Gobet M, Sherr CJ, Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. [PMC free article] [PubMed]
  • Higashio K, Shima N, Goto M, Itagaki Y, Nagao M, Yasuda H, Morinaga T. Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor. Biochem Biophys Res Commun. 1990 Jul 16;170(1):397–404. [PubMed]
  • Hirai Y, Takebe K, Takashina M, Kobayashi S, Takeichi M. Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell. 1992 May 1;69(3):471–481. [PubMed]
  • Iyer A, Kmiecik TE, Park M, Daar I, Blair D, Dunn KJ, Sutrave P, Ihle JN, Bodescot M, Vande Woude GF. Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. Cell Growth Differ. 1990 Feb;1(2):87–95. [PubMed]
  • Kokai Y, Cohen JA, Drebin JA, Greene MI. Stage- and tissue-specific expression of the neu oncogene in rat development. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8498–8501. [PMC free article] [PubMed]
  • Lawson KA. The role of mesenchyme in the morphogenesis and functional differentiation of rat salivary epithelium. J Embryol Exp Morphol. 1972 Jun;27(3):497–513. [PubMed]
  • Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature. 319(6056):743–748. [PubMed]
  • Masters JR. Epithelial-mesenchymal interaction during lung development: the effect of mesenchymal mass. Dev Biol. 1976 Jul 1;51(1):98–108. [PubMed]
  • Mathan M, Moxey PC, Trier JS. Morphogenesis of fetal rat duodenal villi. Am J Anat. 1976 May;146(1):73–92. [PubMed]
  • Miyazawa K, Tsubouchi H, Naka D, Takahashi K, Okigaki M, Arakaki N, Nakayama H, Hirono S, Sakiyama O, Takahashi K, et al. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. [PubMed]
  • Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901–908. [PubMed]
  • Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K, Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. [PubMed]
  • Naldini L, Vigna E, Narsimhan RP, Gaudino G, Zarnegar R, Michalopoulos GK, Comoglio PM. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991 Apr;6(4):501–504. [PubMed]
  • Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan RP, Hartmann G, Zarnegar R, Michalopoulos GK, et al. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 1991 Oct;10(10):2867–2878. [PMC free article] [PubMed]
  • Neckameyer WS, Wang LH. Nucleotide sequence of avian sarcoma virus UR2 and comparison of its transforming gene with other members of the tyrosine protein kinase oncogene family. J Virol. 1985 Mar;53(3):879–884. [PMC free article] [PubMed]
  • Noji S, Tashiro K, Koyama E, Nohno T, Ohyama K, Taniguchi S, Nakamura T. Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. Biochem Biophys Res Commun. 1990 Nov 30;173(1):42–47. [PubMed]
  • Ordahl CP, Le Douarin NM. Two myogenic lineages within the developing somite. Development. 1992 Feb;114(2):339–353. [PubMed]
  • Park M, Dean M, Cooper CS, Schmidt M, O'Brien SJ, Blair DG, Vande Woude GF. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. [PubMed]
  • Park M, Dean M, Kaul K, Braun MJ, Gonda MA, Vande Woude G. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379–6383. [PMC free article] [PubMed]
  • Peles E, Bacus SS, Koski RA, Lu HS, Wen D, Ogden SG, Levy RB, Yarden Y. Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. Cell. 1992 Apr 3;69(1):205–216. [PubMed]
  • Press MF, Cordon-Cardo C, Slamon DJ. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene. 1990 Jul;5(7):953–962. [PubMed]
  • Rosen EM, Meromsky L, Setter E, Vinter DW, Goldberg ID. Purified scatter factor stimulates epithelial and vascular endothelial cell migration. Proc Soc Exp Biol Med. 1990 Oct;195(1):34–43. [PubMed]
  • Rubin JS, Chan AM, Bottaro DP, Burgess WH, Taylor WG, Cech AC, Hirschfield DW, Wong J, Miki T, Finch PW, et al. A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415–419. [PMC free article] [PubMed]
  • Sassoon D, Lyons G, Wright WE, Lin V, Lassar A, Weintraub H, Buckingham M. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature. 1989 Sep 28;341(6240):303–307. [PubMed]
  • Schirmacher P, Geerts A, Pietrangelo A, Dienes HP, Rogler CE. Hepatocyte growth factor/hepatopoietin A is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology. 1992 Jan;15(1):5–11. [PubMed]
  • Shiota G, Rhoads DB, Wang TC, Nakamura T, Schmidt EV. Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):373–377. [PMC free article] [PubMed]
  • Slavkin HC. Embryonic tooth formation. A tool for developmental biology. Oral Sci Rev. 1974;4(0):7–136. [PubMed]
  • Soman NR, Correa P, Ruiz BA, Wogan GN. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4892–4896. [PMC free article] [PubMed]
  • Sonnenberg E, Gödecke A, Walter B, Bladt F, Birchmeier C. Transient and locally restricted expression of the ros1 protooncogene during mouse development. EMBO J. 1991 Dec;10(12):3693–3702. [PMC free article] [PubMed]
  • Sprenger F, Stevens LM, Nüsslein-Volhard C. The Drosophila gene torso encodes a putative receptor tyrosine kinase. Nature. 1989 Apr 6;338(6215):478–483. [PubMed]
  • Stoker M, Perryman M. An epithelial scatter factor released by embryo fibroblasts. J Cell Sci. 1985 Aug;77:209–223. [PubMed]
  • Stoker M, Gherardi E, Perryman M, Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987 May 21;327(6119):239–242. [PubMed]
  • Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. [PubMed]
  • Weidner KM, Behrens J, Vandekerckhove J, Birchmeier W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol. 1990 Nov;111(5 Pt 1):2097–2108. [PMC free article] [PubMed]
  • Weidner KM, Arakaki N, Hartmann G, Vandekerckhove J, Weingart S, Rieder H, Fonatsch C, Tsubouchi H, Hishida T, Daikuhara Y, et al. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001–7005. [PMC free article] [PubMed]
  • Weidner KM, Hartmann G, Naldini L, Comoglio PM, Sachs M, Fonatsch C, Rieder H, Birchmeier W. Molecular characteristics of HGF-SF and its role in cell motility and invasion. EXS. 1993;65:311–328. [PubMed]
  • Weidner KM, Sachs M, Birchmeier W. The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells. J Cell Biol. 1993 Apr;121(1):145–154. [PMC free article] [PubMed]
  • Yamamoto T, Nishida T, Miyajima N, Kawai S, Ooi T, Toyoshima K. The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell. 1983 Nov;35(1):71–78. [PubMed]
  • Zarnegar R, Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 1989 Jun 15;49(12):3314–3320. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...