The Zon Lab

During vertebrate development, ventral mesoderm is induced and specified to form hematopoietic stem cells and later, proliferation and differentiation of the progenitor populations occurs. We executed an expression cloning screen for stem cell inducers of Xenopus by creating a cDNA library just prior to initiation of GATA-1 transcription. This library was segregated into pools, which were injected into embryos at the 1 cell stage. 48 hours later, embryos were scored for excessive blood formation. One pool produced the gene PAX-like Mix.1, which is a homeobox gene that is activin and BMP4 inducible. Mix.1 can transform dorsal mesoderm, which normally would become muscle, into blood. In the zebrafish, we have utilized genetics to define genes that are required for hematopoietic stem cell induction. We have 20 complementation groups of mutants that encompass 4 with stem cell defects, 8 with proliferation problems, 6 with globin expression defects, and 2 with porphyria. We are in the process of position cloning genes in the zebrafish that are represented by these mutants. Isolation of these genes should improve our understanding of hematopoietic stem cell induction during vertebrate embryogenesis.