Development Genes and Evolution

, Volume 213, Issue 7, pp 360–362 | Cite as

Identification and developmental expression of a macrophage stimulating 1/hepatocyte growth factor-like 1 orthologue in the zebrafish

Expression Note


The cytokine Macrophage Stimulating 1 (MST1/MSP/Hepatocyte Growth Factor-Like) is a ligand of the Met-related MST1-Receptor (MST1R/RON). Although MST1-deficient mice are viable, MST1R is essential in mice before gastrulation for implantation, and is a known oncogene in man. Here I report the identification, sequence, chromosomal location and embryonic expression of a novel zebrafish orthologue, termed macrophage stimulating 1 (mst1). mst1 shows a striking restriction of expression to the dorsal side of the embryo prior to gastrulation, and as gastrulation and somitogenesis proceed is expressed sequentially in the presumptive neurectoderm, the notochord, the somites, endodermal cells and in the syncytial yolk. This dynamic pattern is largely conserved in tetrapod vertebrates, suggesting that the appearance of MST1, may have played an early role in the evolution of the vertebrate body plan.


MST1 (Macrophage Stimulating 1) HGFL (Hepatocyte Growth Factor-Like) Zebrafish Neurogenesis Somites 



I would like to thank Steve Wilson and his laboratory, John Postlethwait's laboratory, Sandy Bruce and Heather McAdam.


  1. Aberger F, Schmidt G, Richter K (1996) The Xenopus homologue of Hepatocyte Growth Factor-Like protein is specifically expressed in the presumptive neural plate during gastrulation. Mech Dev 54:23–37CrossRefPubMedGoogle Scholar
  2. Bezerra JA, Carrick TL, Degen JL, Witte D, Degen SJF (1998) Biological effects of targeted inactivation of Hepatocyte Growth Factor-Like protein in mice. J Clin Invest 101(5):1175–1183PubMedGoogle Scholar
  3. Birchmeier C, Gherardi E (1998) Developmental roles of HGF/SF and its receptor, the C-Met tyrosine kinase. Trends Cell Biol 8:404–410CrossRefPubMedGoogle Scholar
  4. Bladt F, Riethmacher D, Isenmann S, Aguzzi A, Birchmeier C (1995) An essential role for the C-Met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376:768–771PubMedGoogle Scholar
  5. Correll PH (1997) Deregulated inflammatory response in mice lacking the STK/RON receptor tyrosine kinase. Genes Funct 1:69–83PubMedGoogle Scholar
  6. Furthauer M, Reifers F, Brand M, Thisse B, Thisse C (2001) Sprouty4 acts in vivo as a feedback-induced antagonist of FGF signaling in zebrafish. Development 128:2175–2186PubMedGoogle Scholar
  7. Gaudino G, Follenzi A, Naldini A, Collesi C, Santoro M, Gallo KA, Godowski PJ, Comoglio PM (1994) Ron is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 13:3524–3532PubMedGoogle Scholar
  8. Greener MJ, Roberts RG (2000) Conservation of components of the dystrophin complex in Drosophila. FEBS Lett 482:13–18CrossRefPubMedGoogle Scholar
  9. Leonard EJ (1997) Biological aspects of macrophage-stimulating protein (MSP) and its receptor. In: Gherardi E (ed) Plasminogen-related growth factors. (Ciba Foundation Symposium 212) Wiley, New York, pp 183–191Google Scholar
  10. Macdonald R, Barth KA, Xu Q, Holder N, Mikkola I, Wilson SW (1995) Midline signalling is required for Pax gene regulation and patterning of the eyes. Development 121:3267–3278PubMedGoogle Scholar
  11. Melby AE, Warga RM, Kimmel CB (1996) Specification of cell fates at the dorsal margin of the zebrafish gastrula. Development 122:2225–2237PubMedGoogle Scholar
  12. Muraoka O, Ichikawa H, Shi H, Okumura S, Taira E, Higuchi H, Hirano T, Hibi M, Miki N (2000) Kheper, a novel ZFH/DeltaEF1 family member, regulates the development of the neuroectoderm of zebrafish (Danio rerio). Dev Biol 228:29–40CrossRefPubMedGoogle Scholar
  13. Nakamura T, Aoki S, Takahashi T, Matsumoto K, Kiyohara T (1996) Cloning and expression of Xenopus HGF-Like Protein (HLP) and Ron/HLP receptor implicate their involvement in early neural development. Biochem Biophys Res Commun 224:564–573CrossRefPubMedGoogle Scholar
  14. Ruiz i Altaba R, Thery C (1996) Involvement of livertine, a hepatocyte growth factor family member, in neural morphogenesis. Mech Dev 60:207–220CrossRefPubMedGoogle Scholar
  15. Slack JMW, Tannahill D (1992) Mechanisms of anteroposterior axis specification in vertebrates: lessons from the amphibians. Development 114:285–302PubMedGoogle Scholar
  16. Streit ACE, Stern CD (1997) Competence for neural induction: HGF/SF, HGFl/MSP and the c-Met receptor. In: Gherardi E (ed) Plasminogen-related growth factors. (Ciba Foundation Symposium 212) Wiley, New York, pp 155–165Google Scholar
  17. Thery C, Sharpe MJ, Batley SJ, Stern CD, Gherardi E (1995) Expression of HGF/SF, HGF1/MSP, and c-Met suggests new functions during early chick development. Developmental Genetics 17:90–101PubMedGoogle Scholar
  18. Uehara Y, Minowa O, Mori C, Shiota K, Kuno J, Noda T, Kitamura N (1995) Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373:702–705PubMedGoogle Scholar
  19. Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R (1994) Identification of the Ron gene product as the receptor for the human macrophage stimulating protein. Science 266:117–119PubMedGoogle Scholar
  20. Woo K, Fraser SE (1997) Specification of the zebrafish nervous system by nonaxial signals. Science 277:254–257CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Comparative and Developmental Genetics Section, MRC Human Genetics UnitWestern General HospitalEdinburghUK

Personalised recommendations