Our goal is to understand the underlying molecular and genetic mechanisms involved in the initiation of hematopoietic differentiation and proliferation during embryogenesis. Towards this goal, we have chosen two of the earliest defined markers of vertebrate hematopoietic development, GATA- l and GATA-2, as entry points into the hematopoietic program of the zebrafish. To identify factors that function to initiate GATA-1 and GATA-2 expression or interact with them to regulate hematopoiesis, we will seek to establish a comprehensive profile of genes specifically co-expressed with GATA-1 and GATA-2; to study the function of these genes through genetic and transgenic analysis; and to elucidate the transcriptional mechanisms controlling hematopoietic expression of GATA-2. We believe that studies from zebrafish should ultimately help us understand how hematopoietic development is controlled in human being.