[PDF][PDF] Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte

SV Outram, A Varas, CV Pepicelli, T Crompton - Immunity, 2000 - cell.com
SV Outram, A Varas, CV Pepicelli, T Crompton
Immunity, 2000cell.com
The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here
we show that sonic hedgehog (Shh) is involved in thymocyte development. Our data suggest
that termination of Hh signaling is necessary for differentiation from CD4− CD8− double-
negative (DN) to CD4+ CD8+ double-positive (DP) thymocyte. Shh is produced by the
thymic stroma, and Patched and Smoothened (Smo), the transmembrane receptors for Shh,
are expressed in DN thymocytes. A neutralizing monoclonal antibody against Shh increases …
Abstract
The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development. Our data suggest that termination of Hh signaling is necessary for differentiation from CD4CD8 double-negative (DN) to CD4+CD8+ double-positive (DP) thymocyte. Shh is produced by the thymic stroma, and Patched and Smoothened (Smo), the transmembrane receptors for Shh, are expressed in DN thymocytes. A neutralizing monoclonal antibody against Shh increases differentiation of DN to DP thymocytes, and Shh protein arrests thymocyte differentiation at the CD25+ DN stage, after T cell receptor β (TCRβ) gene rearrangement. We show that one consequence of pre-TCR signaling is downregulation of Smo, allowing DN thymocytes to proliferate and differentiate.
cell.com