Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus.

Publication Type:

Journal Article

Source:

Blood, Volume 111, Issue 5, p.2615-20 (2008)

Keywords:

2008, Animals, B-Lymphocytes, Basic Helix-Loop-Helix Transcription Factors, Cell Count, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Flow Cytometry Core Facility, Gene Expression Regulation, Humans, Ligands, Membrane Proteins, MICE, Receptors, Notch, Repressor Proteins, Research Trials Office Core Facility - Biostatistics Service, RNA, Messenger, Shared Resources, Stem Cells, T-Lymphocyte Subsets, T-Lymphocytes, Thymus Gland

Abstract:

Notch signaling establishes boundaries in the thymus by inducing T-cell commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thymuses from mice deficient for Notch target Hes5 compared with wild-type littermates. We further show that culture of bone marrow-derived progenitors with increasing densities of purified immobilized Notch ligand (Delta1(ext-IgG)) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded appropriately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to ensure an appropriate outcome in the thymus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required.