Non-Mesodermal (Endodermal) Activators of Hematopoiesis and Vasculogenesis (Stem Cell Development) in the Mouse Embryo
- Mouse Models
- Transgenic Embryo Explant Culture Assays
- Genetically Manipulated Embryonic Stem (ES) Cells
Embryo explant culture studies implicate Indian hedgehog and BMP signaling in activation of embryonic hematopoiesis and vascular development. In these assays, we take apart the embryo and ask what must be added back in order for blood and endothelial cells to form.
Indian hedgehog (Ihh) is confined to the VE during gastrulation and is expressed in a graded manner. Red: anti-Hh staining; eee: extraembryonic ectoderm; epi: epiblast; ps: primitive streak. Dashed lines indicate approximate location of sections shown at right.
Explant culture assays demonstrating that recombinant IHH protein can substitute for VE to activate formation of primitive blood cells (globin-lacZ transgenic embryos) or endothelial cells (Flk1-lacZ embryos) in anterior epiblast pieces, which normally form neural tissue (thus, they are respecified or reprogrammed). Addition of HH-blocking antibody to epiblast + VE recombinants (right) ablates induction of hematopoiesis in these explants.
Translation to clinical practice: We are interested in exploring the possibility that activating or inhibiting the hedgehog signaling pathway may provide a means to treat a variety of human diseases in which these processes are abnormal. Components of the pathway may prove to be good targets for development of new drugs.