Regulation of early T cell development in mouse and human by Notch.
Notch signalling is a critical mediator of T cell development. However, while this signalling pathway is essential, it is not sufficient to induce T cell fate into multipotent hematopoietic precursor cells. Although Notch signalling events are crucial at all of the initial stages of T-lineage differentiation, T cell development also depends on other regulatory factors that are required at precise levels in order to preserve the well-balanced network that drives this process. Miss-expression of one of the factors profoundly perturbs this balance and results in alternative lineage cell fate. In this process, Notch plays an essential role as a gate-keeper of T-lineage fidelity by either enforcing the T cell fate or by inducing cell death if alternative lineages are induced in its presence. Notch also plays a critical role in the further lineage choices that occur within the T cell lineage. Importantly however, this seems to be different between mouse and human. While in the mouse it is clear that TCR-alphabeta T cells are much more dependent on Notch signalling compared to TCR-gammadelta T cells, the requirement for Notch signalling during human T cell development seems to be the opposite for both T cell lineages. Thus, while it is clear that Notch signalling plays a critical role during the early stages of T cell development, further work is essential to delineate the precise molecular network that controls T cell differentiation and this might be different between mouse and human.
Faculty of Medicine and Health Sciences, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, 4 Blok A - B 9000.
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D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D051379:Mice; D051880:Receptors, Notch / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*
D051880:Receptors, Notch