The core-binding factor (CBF) is a heterodimeric transcription factor that plays a significant role in both normal hematopoiesis and leukemia. Chromosomal translocations involving two of the CBF genes (AML1 and CBFB) are associated with a quarter to one third of acute leukemias in humans. CBF is also required for definitive hematopoiesis in mice. The specific developmental step at which CBF is required is not known, but it is presumed to be necessary either for the emergence of definitive multipotent hematopoietic progenitors and/or hematopoietic stem cells (HSCs) in the embryo, the migration of HSCs and/or multipotent progenitors to sites of hematopoiesis, or for differentiation of HSCs or multipotent progenitor cells into functional hematopoietic cells. I would like to study these early steps in embryonic hematopoiesis and determine at which step CBF is required. Specifically, my experimental goals are: 1) to document the appearance and migration of cells expressing the gene encoding a DNA-binding subunit of CBF (Cbfa2) throughout the early stages of definitive hematopoiesis, in the developing mouse embryo, and) document the appearance and migration of hematopoietic cells expressing Cbfa2 in embryos lacking functional CBF, to determine at which step in hematopoiesis CBF is required.
| Yzaguirre, Amanda D; de Bruijn, Marella F T R; Speck, Nancy A (2017) The Role of Runx1 in Embryonic Blood Cell Formation. Adv Exp Med Biol 962:47-64 |
| Tang, Alan T; Choi, Jaesung P; Kotzin, Jonathan J et al. (2017) Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature 545:305-310 |
