Noncanonical Wnt signaling promotes apoptosis in thymocyte development

Huiling Liang, Andrew H. Coles, Zhiqing Zhu, Jennifer Zayas, Roland Jurecic, Joonsoo Kang, Stephen N. Jones

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The Wnt-β-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-Ca2+ 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 αβ 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 β-catenin expression and activity. Conversely, Wnt5a deficiency results in the inhibition of PKC activation, decreased CamKII activity, and elevation of β-catenin amounts in thymocytes. These results indicate that Wnt5a induction of the noncanonical Wnt-Ca2+ pathway alters canonical Wnt signaling and is critical for normal T cell development. JEM

Original languageEnglish (US)
Pages (from-to)3077-3084
Number of pages8
JournalJournal of Experimental Medicine
Volume204
Issue number13
DOIs
StatePublished - Dec 24 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Liang, H., Coles, A. H., Zhu, Z., Zayas, J., Jurecic, R., Kang, J., & Jones, S. N. (2007). Noncanonical Wnt signaling promotes apoptosis in thymocyte development. Journal of Experimental Medicine, 204(13), 3077-3084. https://doi.org/10.1084/jem.20062692