NOTOCHORD REGULATES CARDIAC LINEAGE IN ZEBRAFISH EMBRYOS

We focus here upon regulation by the notochord of myocardial cell fate in zebrafish. Myocardial precursors, defined by lineage tracing in th e living embryo, are in the lateral plate mesoderm adjacent to the not ochord-prechordal plate junction. Interestingly, the anterior end of t he notochord corresponds to the posterior extent of the heart progenit or held, defined by this lineage analysis. This suggested that the not ochord might suppress, or the prechordal plate might enhance, the card iogenic fate. Nkx2.5 expression is, in the zebrafish embryo, closely c orrelated with the position of myocardial precursors, which reside adj acent to the notochord-prechordal plate junction. This expression, how ever, is extinguished in the region posterior to this junction, a regi on normally not contributing cells to the heart. Laser ablation of the notochord tip between the 4-somite and 12-somite stage causes posteri or expansion of the Nkx2.5-expressing region. The ntl mutation of the notochord is associated with posterior extension of Nkx2.5 expression. Lineage tracking, by laser activation of caged fluoresceinated dextra n, confirms that, normally, lateral plate cells next to the notochord do not contribute progeny to the heart. After anterior notochord ablat ion, these cells are redirected to a heart cell fate. These data sugge st that the anterior notochord delimits the posterior extent of the he art held by suppressing the heart cell fate. (C) 1998 Academic Press.