THE T-CELL LEUKEMIA ONCOPROTEIN SCL TAL-1 IS ESSENTIAL FOR DEVELOPMENT OF ALL HEMATOPOIETIC LINEAGES/

The T cell leukemia oncoprotein SCL/tal-1, a basic-helix-loop-helix tr anscription factor, is required for production of embryonic red blood cells in the mouse yolk sac. To define roles in other lineages, we stu died the hematopoietic potential of homozygous mutant SCL/tal-1 -/- em bryonic stem cells upon in vitro differentiation and in vivo in chimer ic mice. Here we show that in the absence of SCL/tal-1, hematopoiesis, including the generation of red cells, myeloid cells, megakaryocytes, mast cells, and both T and B lymphoid cells, is undetectable. These f indings suggest that SCL/tal-1 functions very early in hematopoietic d evelopment, either in specification of ventral mesoderm to a blood cel l fate, or in formation or maintenance of immature progenitors.