Transgenic Expression of Cyclin D1 in Thymic Epithelial Precursors Promotes Epithelial and T Cell Development

Klug, David B.; Crouch, Elizabeth; Carter, Carla; Coghlan, Lezlee G; Conti, Claudio J.; Richie, Ellen R.

doi:10.4049/jimmunol.164.4.1881

Cited by 56 publications

(60 citation statements)

References 31 publications

(31 reference statements)

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“…Most cells express cytokeratins 8 and 18, but a distinct subset also express cytokeratin 5. This subset contains precursors that generate the major population of cytokeratin 5-negative cortical epithelial cells (7,45). Our studies show that, in the hypoplastic thymus of mice deficient for FgfR2-IIIb, many of the epithelial cells fail to progress from the cytokeratin 5/cytokeratin 18-positive stage (Fig.…”

Section: Discussionmentioning

confidence: 90%

Development of the Thymus Requires Signaling Through the Fibroblast Growth Factor Receptor R2-IIIb

Revest

Suniara

Kerr

et al. 2001

The Journal of Immunology

220

197

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Mice deficient for fibroblast growth factor (Fgf)R2-IIIb show a block in thymic growth after embryonic day 12.5, a stage that just precedes its detection in thymic epithelial cells. Fgf7 and Fgf10, the main ligands for FgfR2-IIIb, are expressed in the mesenchyme surrounding the thymic epithelial primordium, and Fgf10-deficient mice also exhibit impaired thymic growth. Hence, Fgf signaling is essential for thymic epithelial proliferation. In addition to the proliferative block, most thymic epithelial cells fail to progress from an immature cytokeratin 5-positive to a cytokeratin 5-negative phenotype. Nevertheless, sufficient epithelial cell differentiation occurs in the severely hypoplastic thymus to allow the development of CD4/CD8-double-positive thymocytes and a very small number of single-positive thymocytes expressing TCRs.

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Section: Discussionmentioning

confidence: 90%

Development of the Thymus Requires Signaling Through the Fibroblast Growth Factor Receptor R2-IIIb

Revest

Suniara

Kerr

et al. 2001

The Journal of Immunology

220

197

View full text Add to dashboard Cite

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“…The present study demonstrates that distinct thymocyte subsets are responsible for changes in the expression patterns of K5 and IL-7 in cortical TECs of the postnatal thymus. We previously demonstrated that downregulation of K5 in the thymic cortex depends on cross talk between K8 ϩ K5 ϩ TEC precursors and T lineage-committed thymocytes (45,67). Thus, K5 is down-regulated in the well-organized cortex of RAG-1-deficient mice, whereas human CD3⑀ transgenic and RAG2/␥ c Ϫ/Ϫ thymi that sustain earlier blocks in thymopoiesis retain a primitive, poorly organized TEC population consisting of K8 ϩ K5 ϩ TEC progenitors.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny and Regulation of IL-7-Expressing Thymic Epithelial Cells

Zamisch

Moore-Scott²,

Su³

et al. 2005

The Journal of Immunology

Self Cite

115

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Epithelial cells in the thymus produce IL-7, an essential cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We identified IL-7-expressing thymic epithelial cells (TECs) throughout ontogeny and in the adult mouse thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.5 and is expressed in a Foxn1-independent pathway. Marked changes occur in the localization and regulation of IL-7-expressing TECs during development. IL-7-expressing TECs are present throughout the early thymic rudiment. In contrast, a major population of IL-7-expressing TECs is localized to the medulla in the adult thymus. Using mouse strains in which thymocyte development is arrested at various stages, we show that fetal and postnatal thymi differ in the frequency and localization of IL-7-expressing TECs. Whereas IL-7 expression is initiated independently of hemopoietic-derived signals during thymic organogenesis, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. Moreover, different thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium, suggesting that despite phenotypic similarities, the cortical TEC compartments of wild-type and RAG-1−/− mice are developmentally and functionally distinct.

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“…In a thymic epithelial cell study, transgenic expression of cyclin-D1, one of the principal target genes of Wnt signalling, has lead to the expansion of the entire epithelial compartment (Klug et al 2000) suggesting that canonical Wnt signalling is involved in thymic epithelial cell proliferation, strengthening the argument, that thymic epithelial development is regulated by Wnt-s. So far, signalling studies have revealed, that Wnt4 can activate both the canonical (Lyons et al 2004) and the non-canonical (Torres et al 1996) (Chang et al 2007;Kim et al 2009) Wnt-pathways.…”

Section: Wnt-s In the Thymusmentioning

confidence: 99%