Reduced thymocyte development in sonic hedgehog knockout embryos

J Immunol. 2004 Feb 15;172(4):2296-306. doi: 10.4049/jimmunol.172.4.2296.

Abstract

The Hedgehog family of secreted intercellular signaling molecules are regulators of patterning and organogenesis during animal development. In this study we provide genetic evidence that Sonic Hedgehog (Shh) has a role in the control of murine T cell development. Analysis of Shh(-/-) mouse embryos revealed that Shh regulates fetal thymus cellularity and thymocyte differentiation. Shh is necessary for expansion of CD4(-)CD8(-) double-negative (DN) thymocytes and for efficient transition from the earliest CD44(+)CD25(-) DN population to the subsequent CD44(+)CD25(+) DN population and from DN to CD4(+)CD8(+) double-positive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • Dose-Response Relationship, Immunologic
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Embryo, Mammalian / immunology*
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Female
  • Fetal Tissue Transplantation / immunology
  • Fetus
  • Hedgehog Proteins
  • Liver Transplantation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Receptors, Interleukin-2 / biosynthesis
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Thymus Gland / pathology*
  • Thymus Gland / radiation effects
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics*
  • Trans-Activators / pharmacology

Substances

  • Hedgehog Proteins
  • Receptors, Interleukin-2
  • Trans-Activators