Department of Cell Biology; Department of Pathology; Department of Cancer Biology
Animals; *Apoptosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Calcium; Cell Proliferation; Cell Separation; *Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Models, Biological; Signal Transduction; Thymus Gland; Wnt Proteins
Life Sciences | Medicine and Health Sciences
The Wnt-beta-catenin signaling pathway has been shown to govern T cell development by regulating the growth and survival of progenitor T cells and immature thymocytes. We explore the role of noncanonical, Wnt-Ca(2+) signaling in fetal T cell development by analyzing mice deficient for Wnt5a. Our findings reveal that Wnt5a produced in the thymic stromal epithelium does not alter the development of progenitor thymocytes, but regulates the survival of alphabeta lineage thymocytes. Loss of Wnt5a down-regulates Bax expression, promotes Bcl-2 expression, and inhibits apoptosis of CD4(+)CD8(+) thymocytes, whereas exogenous Wnt5a increases apoptosis of fetal thymocytes in culture. Furthermore, Wnt5a overexpression increases apoptosis in T cells in vitro and increases protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII) activity while inhibiting beta-catenin expression and activity. Conversely, Wnt5a deficiency results in the inhibition of PKC activation, decreased CamKII activity, and elevation of beta-catenin amounts in thymocytes. These results indicate that Wnt5a induction of the noncanonical Wnt-Ca(2+) pathway alters canonical Wnt signaling and is critical for normal T cell development.
DOI of Published Version
J Exp Med. 2007 Dec 24;204(13):3077-84. Epub 2007 Dec 10. Link to article on publisher's site
The Journal of experimental medicine
Liang, Huiling; Coles, Andrew H.; Zhu, Zhiqing; Zayas, Jennifer; Jurecic, Roland; Kang, Joonsoo; and Jones, Stephen N., "Noncanonical Wnt signaling promotes apoptosis in thymocyte development" (2007). Open Access Articles. 1285.