REGULATION IN THE HEART FIELD OF ZEBRAFISH

In many vertebrates, removal of early embryonic heart precursors can b e repaired, leaving the heart and embryo without visible deficit. One possibility is that this 'regulation' involves a cell fate sn itch whe reby cells, perhaps in regions surrounding normal progenitors, are red irected to the heart cell fate. How ever, the lineage and spatial rela tionships between cells that are normal heart progenitors and those th at can assume that role after injury are not known, nor are their mole cular distinctions. We have adapted a laser-activated technique to lab el single or small patches of cells in the lateral plate mesoderm of t he zebrafish and to track their subsequent lineage. We find that the h eart precursor cells are clustered in a region adjacent to the prechor dal plate, just anterior to the notochord tip. Complete unilateral abl ation of all heart precursors with a laser does not disrupt heart deve lopment, if performed before the 18-somite stage. By combining extirpa tion of the heart precursors with cell labeling, we find that cells an terior to the normal cardiogenic compartments constitute the source of regulatory cells that compensate for the loss of the progenitors. One of the earliest embryonic markers of the premyocardial cells is the d ivergent homeodomain gene, Nkx2.5. Interestingly, normal cardiogenic p rogenitors derive from only the anterior half of the Nkx2.5-expressing region in the lateral plate mesoderm. The posterior half, adjacent to the notochord, does not include cardiac progenitors and the posterior Nkx2.5'-expressing cells do not contribute to the heart, even after a blation of the normal cardiogenic region. The cells that can acquire a cardiac cell fate after injury to the normal progenitors also reside near the prechordal plate, but anterior to the Nkx2.5-expressing domai n. Normally they give rise to head mesenchyme. They share with cardiac progenitors early expression of GATA 4. The location of the different elements of the cardiac field, and their response to injury, suggests that the prechordal plate supports and/or the notochord suppresses th e cardiac fate.