RUNX1 is one of three mammalian RUNX genes that control multiple aspects of embryonic development and are responsible for the pathogenesis of many human diseases. RUNX1 plays major roles in the development of nociceptive sensory neurons in addition to hematopoietic stem cells (HSC) with the exception of the erythroid lineage. During development, Notch signals mediate RUNX1 induction with SCL/GATA/Ets factors, and Wnt signals potentially cooperate with RUNX1 to facilitate adult HSC expansion via cooperative induction of cyclin D, cdk4, and other cell cycle regulators. In turn, RUNX1 regulates cell cycle transitions dependent on functional/physical interactions with other proteins such as HDAC1 and -3, mSin3A, p300, SMAD proteins, and LEF/TCF.