Miles-apart-mediated regulation of cell-fibronectin interaction and myocardial migration in zebrafish

Takaaki Matsui, Ángel Raya, Carles Callol-Massot, Yasuhiko Kawakami, Isao Oishi, Concepcion Rodriguez-Esteban, Juan Carlos Izpisúa Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)S77-S82
JournalNature Clinical Practice Cardiovascular Medicine
Issue numberSUPPL. 1
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Miles-apart-mediated regulation of cell-fibronectin interaction and myocardial migration in zebrafish'. Together they form a unique fingerprint.

Cite this