Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus

Abdeljabar El Andaloussi; Stephanie Graves; Fanyong Meng; Malay Mandal; Mona Mashayekhi; Iannis Aifantis

doi:10.1038/ni1313

Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus

Nat Immunol. 2006 Apr;7(4):418-26. doi: 10.1038/ni1313. Epub 2006 Mar 5.

Authors

Abdeljabar El Andaloussi¹, Stephanie Graves, Fanyong Meng, Malay Mandal, Mona Mashayekhi, Iannis Aifantis

Affiliation

¹ Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA.

PMID: 16518394
DOI: 10.1038/ni1313

Abstract

Commitment of hematopoietic progenitors to the T cell lineage requires the integration of multiple signaling pathways. Evidence has suggested involvement of hedgehog (Hh) signaling in T cell differentiation through its signal transducer smoothened (Smo). However, the precise function of the Hh pathway remains controversial, mainly because T cell-specific in vivo genetic models have not been used. Using pre-T cell-specific, mature T cell-specific and poly(I).poly(C)-inducible deletions of Smo and antagonists of Smo signaling, we report here that Hh is an essential positive regulator of T cell progenitor differentiation. Furthermore, we localize Hh function to a stage preceding pre-T cell receptor signaling, connect Smo signaling to the activity of the Gli1 and Gli2 transcription factors and demonstrate that Hh affects regulators of thymocyte survival and proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle / immunology
Cell Differentiation / immunology
DNA, Complementary / chemistry
DNA, Complementary / genetics
Hedgehog Proteins
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / immunology*
Hematopoietic Stem Cells / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Polymerase Chain Reaction
Receptor, Notch1 / immunology
Receptors, G-Protein-Coupled / antagonists & inhibitors
Receptors, G-Protein-Coupled / immunology
Signal Transduction
Smoothened Receptor
Specific Pathogen-Free Organisms
T-Lymphocytes / cytology
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Thymus Gland / cytology
Thymus Gland / immunology*
Thymus Gland / metabolism
Trans-Activators / genetics
Trans-Activators / immunology*
Trans-Activators / metabolism
Veratrum Alkaloids / pharmacology

Substances

DNA, Complementary
Hedgehog Proteins
Notch1 protein, mouse
Receptor, Notch1
Receptors, G-Protein-Coupled
Smo protein, mouse
Smoothened Receptor
Trans-Activators
Veratrum Alkaloids
cyclopamine