Talk:Thymus Development

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Cite this page: Hill, M.A. (2024, March 28) Embryology Thymus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Thymus_Development

2010

A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2

Dev Dyn. 2010 Jul;239(7):1988-94.

Michell AC, Bragança J, Broadbent C, Joyce B, Franklyn A, Schneider JE, Bhattacharya S, Bamforth SD.

Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, United Kingdom. Abstract Deletion of the transcriptional modulator Cited2 in the mouse results in embryonic lethality, cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects, all seen with a varying degree of penetrance. The phenotypic heterogeneity, observed on different genetic backgrounds, indicates the existence of both genetic and environmental modifiers. Mice lacking the LIM domain-containing protein Lmo4 share specific phenotypes with Cited2 null embryos, such as embryonic lethality, cranial ganglia fusion, and exencephaly. These shared phenotypes suggested that Lmo4 may be a potential genetic modifier of the Cited2 phenotype. Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of expression of a common target gene, Tbx1, which is necessary for normal thymus development.

(c) 2010 Wiley-Liss, Inc. PMID: 20549734

2009

Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development

Blood. 2009 Mar 26;113(13):2976-87. Epub 2009 Jan 22.

Sultana DA, Tomita S, Hamada M, Iwanaga Y, Kitahama Y, Khang NV, Hirai S, Ohigashi I, Nitta S, Amagai T, Takahashi S, Takahama Y.

Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.

Abstract

The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are expressed in the third pharyngeal pouch, which contains thymic primordium. Polymerase chain reaction (PCR)-based cDNA subtraction screening for genes expressed in microdissected tissues of the third pharyngeal pouch rather than the second pharyngeal arch yielded one transcription factor, MafB, which was predominantly expressed in CD45(-)IA(-)PDGFRalpha(+) mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1-deficient nude mice. Interestingly, the number of CD45(+) cells that initially accumulated in the embryonic thymus was significantly decreased in MafB-deficient mice. Alterations of gene expression in the embryonic thymi of MafB-deficient mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in the embryonic thymus.

PMID: 19164599

2008

Neural crest origin of perivascular mesenchyme in the adult thymus

J Immunol. 2008 Apr 15;180(8):5344-51.

Müller SM, Stolt CC, Terszowski G, Blum C, Amagai T, Kessaris N, Iannarelli P, Richardson WD, Wegner M, Rodewald HR.

Institute for Immunology, University of Ulm, Ulm, Germany.

Abstract

The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-NC interaction is crucial for thymus development, but it is not known how NC supports thymus development or whether NC cells or their progeny make any significant contribution to the adult thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-independent mesenchymal cell population. These mesenchymal cells expressed vascular endothelial growth factor-A, and contributed to thymus vascularization. These data suggested a physical or functional association with thymic blood vessels, but the origin, location in the thymus, and function of these stromal cells remained unknown. Using a transgenic mouse expressing Cre recombinase in premigratory NC (Sox10-Cre), we have now fate-mapped the majority of these adult mesenchymal cells to a NC origin. NC-derived cells represent tightly vessel-associated pericytes that are sandwiched between endothelium and epithelium along the entire thymus vasculature. The ontogenetic, phenotypic, and positional definition of this distinct perivascular mesenchymal compartment provides a cellular basis for the role of NC in thymus development and possibly maintenance, and might be useful to address properties of the endothelial-epithelial barrier in the adult thymus.

PMID: 18390716

http://www.jimmunol.org/content/180/8/5344.long

2006

Cellular and molecular events during early thymus development

Holländer G, Gill J, Zuklys S, Iwanami N, Liu C, Takahama Y. Immunol Rev. 2006 Feb;209:28-46. Review.

The thymic stromal compartment consists of several cell types that collectively enable the attraction, survival, expansion, migration, and differentiation of T-cell precursors. The thymic epithelial cells constitute the most abundant cell type of the thymic microenvironment and can be differentiated into morphologically, phenotypically, and functionally separate subpopulations of the postnatal thymus. All thymic epithelial cells are derived from the endodermal lining of the third pharyngeal pouch. Very soon after the formation of a thymus primordium and prior to its vascularization, thymic epithelial cells orchestrate the first steps of intrathymic T-cell development, including the attraction of lymphoid precursor cells to the thymic microenvironment. The correct segmentation of pharyngeal epithelial cells and their subsequent crosstalk with cells in the pharyngeal arches are critical prerequisites for the formation of a thymus anlage. Mutations in several transcription factors and their target genes have been informative to detail some of the complex mechanisms that control the development of the thymus anlage.

PMID: 16448532