T cells develop from multipotent progenitors in the thymus. Initially, these progenitors can generate myeloid cells, B lymphocytes and T cells but, as differentiation proceeds, they become committed to the T-cell lineage. On , Marissa Morales Del Real and Ellen Rothenberg investigate the regulatory network that controls this process. Previous studies have shown that the decision to become a T cell can be opposed by the myeloid cell transcription factor PU.1 but that exposure to Notch signalling determines the developmental outcome of expressing PU.1. The researchers now show that Notch signalling does not inactivate the PU.1 protein but instead re-channels its transcriptional effects to maintain a T-cell transcriptional network. They describe two branches of this network - one that involves basic helix-loop-helix E proteins in a positive-feedback loop with Notch, and one in which PU.1 can inhibit T-cell transcription factor genes such as Gata3 only if Notch signalling is absent. Together, these results provide new insights into the complex architecture of a lymphomyeloid developmental switch.
