Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2178K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liang, H. Articles by Jones, S. N. Search for Related Content PubMed PubMed Citation Articles by Liang, H. Articles by Jones, S. N. Social Bookmarking                      What's this?

Departments of ¹ Cell Biology, ² Pathology, and ³ Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01545
⁴ Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136
⁵ Charles River Laboratories, Wilmington, MA 10877

CORRESPONDENCE Stephen N. Jones: stephen.jones{at}umassmed.edu

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 β 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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Yang, H., Youm, Y.-H., Sun, Y., Rim, J.-S., Galban, C. J., Vandanmagsar, B., Dixit, V. D. (2009). Axin expression in thymic stromal cells contributes to an age-related increase in thymic adiposity and is associated with reduced thymopoiesis independently of ghrelin signaling. J. Leukoc. Biol. 85: 928-938 [Abstract] [Full Text]  
• Sultana, D. A., Tomita, S., Hamada, M., Iwanaga, Y., Kitahama, Y., Van Khang, N., Hirai, S., Ohigashi, I., Nitta, S., Amagai, T., Takahashi, S., Takahama, Y. (2009). Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development. Blood 113: 2976-2987 [Abstract] [Full Text]  
• Malhotra, S., Baba, Y., Garrett, K. P., Staal, F. J. T., Gerstein, R., Kincade, P. W. (2008). Contrasting Responses of Lymphoid Progenitors to Canonical and Noncanonical Wnt Signals. J. Immunol. 181: 3955-3964 [Abstract] [Full Text]  
• 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. JCB 179: i17-i17 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS