Inhibition of E47 activity by Notch. E47 is a basic helix-loop-helix protein that is necessary for B cell development. Although E47 is ubiquitously expressed, activity is specifically regulated in B cells by mechansims that remain unclear. Our preliminary studies indicate that E47 is inhibited by activation of the transmembrane receptor, Notch. In vertabrates and invertabrates, Notch is involved in cell fate decisions in multiple lineages and activity correlates with an immature developmental status. The goal of this research is to examine the ability of Notch to inhibit endogenous E47 activity in B cells and determine the signaling components required to mediate E47 inhibition. Established and novel Notch signaling effectors will be examined. The physiological relevance of Notch activity will be assessed by expressing Notch ectopically in the B cell compartment of mice and monitoring B lymphopoiesis.
