Hedgehog Signalling in T Lymphocyte Development
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T cell development occurs in the thymus, which is seeded by multipotential lymphocyte progenitor cells. These cells then move through a sequence of clearly defined developmental stages at the end of which they become a fully functional mature T cell. For correct organogenesis and T cell development to occur the thymic stroma and the developing thymocytes must interact with one another. Thymocyte development is regulated by factors produced by the thymic stroma. Sonic hedgehog (Shh) is secreted by the thymic stroma and Patched (Ptc), Smoothened (Smo) and the Gli transcription factors are expressed by thymocytes. In the mouse, Shh is involved in the proliferation and efficient progression through the differentiation process, as well as maintaining normal thymic cellularity. In the human, Shh signals to progenitor cells in a paracrine fashion to instruct these cells to maintain the precursor cell pool by increasing their cell viability and inhibiting their expansion and concomitant progression to the next stage in development. Thus, Shh plays an important role in T cell development in both human and mouse.
KeywordsSonic Hedgehog Hedgehog Signalling Thymic Epithelial Cell Human Thymus Thymocyte Development
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