Cell type specific expression of these isoforms would then dictate the synthesis of a particular array of GAGs. We have looked at this interaction by employing antisense oligonucleotides under in vitro and in vivo conditions as well as overexpressing various proto-oncogenes. Our results demonstrate that c-Myb is a critical target for HSPGs. It is unclear how these biologic events are coordinately regulated. In studying an embryologic system in which the thrombomodulin and von Willebrand factor gene transcription is initiated together with the appearance of other endothelial cell gene products, and an adult system in which cytokines induce transcription of thrombomodulin as well as von Willebrand factor in association with the expression of other endothelial cell receptors, we have elucidated regulatory circuits that control heart specific angiogenesis.
Megakaryocytes originate from stem cells of the bone marrow.
Specific granules arise containing cofactors which accelerate blood coagulation, adhesive proteins which facilitate cell-cell interactions, and growth factors which stimulate wound healing. Once cytoplasmic maturation terminates, megakaryocytes fragment into small anucleate platelets which circulate within the blood. Also, we and other groups have isolated thrombopoietin, the critical growth factor that regulates megakaryocytopoiesis. Our knowledge of the PF4 gene and of thrombopoietin is used to define the cellular pathway by which stem cells are committed to megakaryocytes, subsequent steps of cytoplasmic maturation and fragmentation, and the mechanism by which platelet levels control the extent of megakaryocytopoiesis. . Graduates of the Program of Excellence, Rosenberg Lab . .