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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

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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

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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.

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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

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  1. Takaaki Matsui
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  7. Juan Carlos Izpisúa Belmonte
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Correspondence to Juan Carlos Izpisúa Belmonte.

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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

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