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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Dose-Response Relationship, Immunologic
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Embryo, Mammalian / immunology*
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Embryo, Mammalian / metabolism
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Embryo, Mammalian / pathology
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Female
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Fetal Tissue Transplantation / immunology
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Fetus
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Hedgehog Proteins
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Liver Transplantation / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Organ Culture Techniques
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Receptors, Interleukin-2 / biosynthesis
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology*
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Thymus Gland / immunology*
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Thymus Gland / metabolism
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Thymus Gland / pathology*
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Thymus Gland / radiation effects
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Trans-Activators / deficiency*
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Trans-Activators / genetics*
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Trans-Activators / pharmacology
Substances
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Hedgehog Proteins
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Receptors, Interleukin-2
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Trans-Activators