THE CLOCHE AND SPADETAIL GENES DIFFERENTIALLY AFFECT HEMATOPOIESIS AND VASCULOGENESIS

In vertebrates, hematopoietic and vascular progenitors develop from ve ntral mesoderm. The first primitive wave of hematopoiesis yields embry onic red blood cells, whereas progenitor cells of subsequent definitiv e waves form all hematopoietic cell Lineages. In this report we examin e the development of hematopoietic and vasculogenic cells in normal ze brafish and characterize defects in cloche and spadetail mutant embryo s. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have be en cloned and characterized in this study. Expression of these genes i dentifies embryonic regions that contain hematopoietic and vascular pr ogenitor cells. The expression of c-myb also identifies definitive hem atopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrat es that c-myb is not required for primitive erythropoiesis in zebrafis h even though it is expressed in these cells. Both cloche and spadetai l mutant embryos have defects in primitive hematopoiesis and definitiv e hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular me chanisms that regulate hematopoiesis and vasculogenesis have been cons erved throughout vertebrate evolution and the clo and spt genes are ke y regulators of these programs. (C) 1998 Academic Press.