Fate mapping embryonic blood in zebrafish: multi- and unipotential lineages are segregated at gastrulation

Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages via progenitors that are unipotent for single blood lineages. Using a variety of in vivo cell-tracing techniques, we show that primitive blood in zebrafish derives from two different progenitor types. On the dorsal gastrula, blood progenitors are unipotential cells that divide infrequently, populate the rostral blood islands, and differentiate into macrophages. In contrast, on the ventral gastrula, blood progenitors are multipotential cells with rapid cell cycles; populate the intermediate cell mass; and differentiate into erythrocytes, neutrophils, and thrombocytes. Our results demonstrate the existence of primitive hematopoietic progenitors that are segregated very early in development and that are specified to produce either a unipotent or a multipotent blood cell lineage.