Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

miles-apart-Mediated regulation of cell–fibronectin interaction and myocardial migration in zebrafish

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S77–S82 (2007)Cite this article

Abstract

The migration of myocardial precursor cells towards the embryonic midline underlies the formation of the heart tube and is a key process of heart organogenesis. The zebrafish mutation miles-apart (mil), which affects the gene encoding a sphingosine-1-phosphate receptor, is characterized by defective migration of myocardial precursor cells and results in the formation of two laterally positioned hearts, a condition known as cardia bifida. The mechanism that disrupts myocardial migration in mil mutants remains largely unclear. To investigate how mil regulates this process, here we analyze the interactions between mil and other mediators of myocardial migration. We show that mil function is associated with the other known cardia bifida locus, natter/fibronectin (nat/fn), which encodes fibronectin, a major component of the extracellular matrix, in the control of myocardial migration. By using a primary culture system of embryonic zebrafish cells, we also show that signaling from the sphingosine-1-phosphate receptor regulates cell–fibronectin interactions in zebrafish. In addition, localized inhibition and activation of cell–fibronectin interactions during the stages of myocardial migration reveal that the temporal regulation of cell–fibronectin interaction by mil is required for proper myocardial migration. Our study reveals novel functional links between sphingosine-1-phosphate receptor signaling and cell–fibronectin interaction in the control of myocardial migration during zebrafish heart organogenesis.

Key Points

  • Myocardial migration is a key process of heart organogenesis

  • The mechanism underlying this process remains largely unknown

  • We analyzed this mechanism and found a positive interaction between miles apart and natter/fibronectin functions in the control of myocardial migration during zebrafish heart organogenesis

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Effects of loss-of-function or gain-of-function of fibronectin (Fn) on myocardial migration
Figure 2: Downregulation of fibronectin function leads to severe cardia bifida in miles apart (mil)-mutant embryos
Figure 3: miles apart (mil) specifically controls cell–fibronectin interactions

Similar content being viewed by others

References

  1. Stainier DY (2001) Zebrafish genetics and vertebrate heart formation. Nat Rev Genet 2: 39–48

    Article  CAS  Google Scholar 

  2. Yelon D et al. (2000) The bHLH transcription factor hand2 plays parallel roles in zebrafish heart and pectoral fin development. Development 127: 2573–2582

    CAS  PubMed  Google Scholar 

  3. Reiter JF et al. (1999) Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev 13: 2983–2995

    Article  CAS  Google Scholar 

  4. Schier AF et al. (1997) The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development 124: 327–342

    CAS  PubMed  Google Scholar 

  5. Kikuchi Y et al. (2000) The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors. Genes Dev 14: 1279–1289

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Alexander J et al. (1999) casanova plays an early and essential role in endoderm formation in zebrafish. Dev Biol 215: 343–357

    Article  CAS  Google Scholar 

  7. Komada M and Soriano P (1999) Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Genes Dev 13: 1475–1485

    Article  CAS  Google Scholar 

  8. Li S et al. (2004) Advanced cardiac morphogenesis does not require heart tube fusion. Science 305: 1619–1622

    Article  CAS  Google Scholar 

  9. Withington S et al. (2001) Foregut endoderm is required at head process stages for anteriormost neural patterning in chick. Development 128: 309–320

    CAS  PubMed  Google Scholar 

  10. Matsui T et al. (2005) Noncanonical Wnt signaling regulates midline convergence of organ primordia during zebrafish development. Genes Dev 19: 164–175

    Article  CAS  Google Scholar 

  11. Kupperman E et al. (2000) A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development. Nature 406: 192–195

    Article  CAS  Google Scholar 

  12. Trinh LA and Stainier DY (2004) Fibronectin regulates epithelial organization during myocardial migration in zebrafish. Dev Cell 6: 371–382

    Article  CAS  Google Scholar 

  13. Ng JK et al. (2002) The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10. Development 129: 5161–5170

    CAS  PubMed  Google Scholar 

  14. George EL et al. (1993) Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119: 1079–1091

    CAS  PubMed  Google Scholar 

  15. Linask KK and Lash JW (1988) A role for fibronectin in the migration of avian precardiac cells. I. Dose-dependent effects of fibronectin antibody. Dev Biol 129: 315–323

    Article  CAS  Google Scholar 

  16. Zhang Q et al. (1999) Sphingosine 1-phosphate stimulates fibronectin matrix assembly through a Rho-dependent signal pathway. Blood 93: 2984–2990

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M Schwarz for help in preparing the manuscript. T Matsui is supported by a Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship for Research Abroad. Á Raya was partially supported by a postdoctoral fellowship from Fundacion Inbiomed, Spain. C Callol-Massot and C Rodriguez-Esteban were partially supported by Biobide. I Oishi is supported by a postdoctoral fellowship from Centre de Medicina Regenerativa de Barcelona (CMRB), Spain. This work was supported by grants from the National Institutes of Health, Fundacion Cellex, and the G Harold and Leila Y Mathers Charitable Foundation to JC Izpisúa Belmonte.

Author information

Authors and Affiliations

  1. T Matsui is an Assistant Professor in the Gene Regulation Research Laboratory at the Nara Institute of Science and Technology, Ikoma, Japan.,

    Takaaki Matsui

  2. Á Raya is an ICREA Research Professor and Scientific Coordinator, I Oishi is a Research Associate, and JC Izpisúa Belmonte is Director of the Center of Regenerative Medicine in Barcelona, Barcelona, Spain.,

    Ángel Raya, Isao Oishi & Juan Carlos Izpisúa Belmonte

  3. C Callol-Massot and I Oishi are Research Associates, Y Kawakami is a Staff Scientist, C Rodriguez-Esteban is a Senior Research Associate, and JC Izpisúa Belmonte a Professor in the Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA.,

    Carles Callol-Massot, Yasuhiko Kawakami, Isao Oishi, Concepcion Rodriguez-Esteban & Juan Carlos Izpisúa Belmonte

  4. C Callol-Massot is also a Scientific Director at Biobide, Parque Tecnologico de San Sebastian, Donostia, Spain.,

    Carles Callol-Massot

Authors
  1. Takaaki Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ángel Raya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carles Callol-Massot
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuhiko Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isao Oishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Concepcion Rodriguez-Esteban
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Carlos Izpisúa Belmonte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan Carlos Izpisúa Belmonte.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsui, T., Raya, Á., Callol-Massot, C. et al. miles-apart-Mediated regulation of cell–fibronectin interaction and myocardial migration in zebrafish. Nat Rev Cardiol 4 (Suppl 1), S77–S82 (2007). https://doi.org/10.1038/ncpcardio0764

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpcardio0764

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing