Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation

doi:10.1006/smim.2000.0263

Seminars in Immunology

Volume 12, Issue 5, October 2000, Pages 421-428

https://doi.org/10.1006/smim.2000.0263 Get rights and content

Abstract

In the mature thymus, thymocyte maturation depends on interactions with different thymic epithelial subtypes in a three-dimensional thymic architecture. However, the molecular mechanisms that generate these epithelial subtypes are not well understood. Evidence is accumulating that during fetal thymus development, epithelial cells differentiate by successive interactions with differentiating thymocytes. This review presents fetal thymus development as a process of organogenesis, the main function of which is to promote thymic epithelial cell differentiation and the generation of a functional thymic microenvironment. In this model, endoderm-derived epithelial cells are the driving force in generating the thymic primordium, with hematopoietic cells providing later signals that organize and pattern the developing thymus.

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The thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence, resulting in a severe reduction or absence of naive T-cell output. The ability to generate a patient-derived human thymus would provide an attractive research platform and enable the development of novel cell therapies.
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Regular ArticleThymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation

Abstract

Studies on the thymus of the mammal XIV: Histology and histochemistry of embryonic and early postnatal thymuses of C57BL/6 and AKR strain mice

Am J Anat

Experimental studies on the development of the thymus

J Exp Med

Tissue interaction in the development of thymus lymphocytes

J Exp Med

Tracing of cells of the avian thymus through embryonic life in interspecific chimeras

J Exp Med

Development of thymus, parathyroids, and ultimobranchial bodies in NMRI and Nude mice

Am J Anat

Ontogeny of primary lymphoid organs and lymphoid stem cells

Am J Anat

Development in the thymus: it takes two to tango

Immunol Today

A common stem cell for murine cortical and medullary thymic epithelial cells?

Dev Immunol

Thymic medulla epithelial cells acquire specific markers by post-mitotic maturation

Dev Immunol

The human thymic microenvironment: new approaches to functional analysis

Semin Immunol

Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos

J Embryol Exp Morph

Thymus ontogeny studied in interspecific chimeras

Fate of the mammalian cardiac neural crest

Development

Dependence of thymus development on derivatives of the neural crest

Science

Pax3 is required for cardiac neural crest migration in the mouse: evidence from the splotch (Sp2H) mutant

Development

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Eur J Immunol

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Eur J Immunol

Epidermal growth factor can replace thymic mesenchyme in induction of embryonic thymus morphogenesis in vitro

Eur J Immunol

An essential role for thymic mesenchyme in early T cell development

J Exp Med

Morphogenetic interactions in the development of the mouse thymus gland

Dev Biol

MHC class II-positive epithelium and mesenchyme cells are both required for T-cell development in the thymus

Nature

Hox genes in vertebrate development

Cell

The role of hoxa-3 in mouse thymus and thyroid development

Development

Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox genehox-1.5

Nature

Hox group 3 paralogs regulate the development and migration of the thymus, thyroid and parathyroid glands

Dev Biol

Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1

Dev Biol

PAX genes

Curr Opin Gen Dev

Pax genes and organogenesis

Bioessays

Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities

Genes Dev

Undulated phenotypes suggest a role of Pax-1 for the development of vertebral and extravertebral structures

Dev Biol

Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation

Development

Regular Article
Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation