Integrated morphogen signal inputs in γδ versus αβ T-cell differentiation

Morphogens, a class of secreted proteins that regulate gene expression in a concentration-dependent manner, are responsible for directing nearly all lineage fate choices during embryogenesis. In the thymus, morphogen signal pathways consisting of WNT, Hedgehog, and the transforming growth factor-beta superfamily are active and have been implicated in various developmental processes including proliferation, survival, and differentiation of maturing thymocytes. Intriguingly, it has been inferred that some of these morphogen signal pathways differentially affect gamma delta and alpha beta T-cell development or maintenance, but their role in T-cell lineage commitment has not been directly probed. We have recently identified a modulator of morphogen signaling that significantly influences binary gamma delta versus alpha beta T-cell lineage diversification. In this review, we summarize functions of morphogens in the thymus and provide a highly speculative model of integrated morphogen signals, potentially directing the gamma delta versus alpha beta T-cell fate determination process.