HEMATOPOIESIS AND STEM CELLS Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus

Notch signaling establishes boundaries in the thymus by inducing T-cell commit-ment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thy-muses from mice deficient for Notch tar-get Hes5 compared with wild-type litter-mates. We further show that culture of bone marrow–derived progenitors with increasing densities of purified immobi-lized Notch ligand (Delta1ext-IgG) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded appropri-ately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to en-sure an appropriate outcome in the thy-mus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required. (Blood