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 language | English |
|---|---|
| Pages (from-to) | 3077-3084 |
| Number of pages | 8 |
| Journal | Journal of Experimental Medicine |
| Volume | 204 |
| Issue number | 13 |
| DOIs | |
| State | Published - Dec 24 2007 |
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ASJC Scopus subject areas
- Immunology
Cite this
Noncanonical Wnt signaling promotes apoptosis in thymocyte development. / Liang, Huiling; Coles, Andrew H.; Zhu, Zhiqing; Zayas, Jennifer; Jurecic, Roland; Kang, Joonsoo; Jones, Stephen N.
In: Journal of Experimental Medicine, Vol. 204, No. 13, 24.12.2007, p. 3077-3084.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Noncanonical Wnt signaling promotes apoptosis in thymocyte development
AU - Liang, Huiling
AU - Coles, Andrew H.
AU - Zhu, Zhiqing
AU - Zayas, Jennifer
AU - Jurecic, Roland
AU - Kang, Joonsoo
AU - Jones, Stephen N.
PY - 2007/12/24
Y1 - 2007/12/24
N2 - 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
AB - 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
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U2 - 10.1084/jem.20062692
DO - 10.1084/jem.20062692
M3 - Article
VL - 204
SP - 3077
EP - 3084
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 13
ER -