SCL SPECIFIES HEMATOPOIETIC MESODERM IN XENOPUS EMBRYOS

Targeted gene disruption experiments in the mouse have demonstrated an absolute requirement for several transcription factors for the develo pment of hematopoietic progenitors during embryogenesis. Disruption of the basic helix-loop-helix gene SCL (stem cell leukemia) causes a blo ck early in the hematopoietic program with defects in all hematopoieti c lineages. To understand how SCL participates in the organogenesis of blood, we have isolated cDNAs encoding Xenopus SCL and characterized the function of SCI, during embryogenesis. We demonstrate that SCL is expressed in ventral mesoderm early in embryogenesis, SCL expression i s induced by BMP-4, and a dominant negative BMP-4 receptor inhibits SC L expression in the ventral region of the embryo. Expression of SCL in either bFGF-treated animal pole explants or dorsal marginal zone expl ants leads to the expression of globin protein. Furthermore, over-expr ession of SCL does not alter normal dorsal-ventral patterning in the e mbryo, indicating that SCL acts to specify mesoderm to a hematopoietic fate after inductive and patterning events have occurred. We propose that SCL is both necessary and sufficient to specify hematopoietic mes oderm, and that it has a similar role in specifying hematopoietic cell fate as MyoD has in specifying muscle cell fate.