Imperial College London
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DrRobertKypta

Faculty of Medicine, Department of Surgery & Cancer

Senior Lecturer in Cancer Biology
 
 
 
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Contact

 

r.kypta Website

 
 
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Location

 

4007Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bengoa-Vergniory:2014:10.1002/stem.1807,
author = {Bengoa-Vergniory, N and Gorrono-Etxebarria, I and Gonzalez-Salazar, I and Kypta, RM},
doi = {10.1002/stem.1807},
journal = {Stem Cells},
pages = {3196--3208},
title = {A switch from canonical to noncanonical Wnt signaling mediates early differentiation of human neural stem cells},
url = {http://dx.doi.org/10.1002/stem.1807},
volume = {32},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Wnt/β-catenin signaling is essential for neurogenesis but less is known about β-catenin-independent Wnt signals. We show here that Wnt/activator protein-1 (AP-1) signaling drives differentiation of human embryonic stem cell and induced pluripotent stem cell-derived neural progenitor cells. Neuronal differentiation was accompanied by a reduction in β-catenin/Tcf-dependent transcription and target gene expression, increased levels and/or phosphorylation of activating transcription factor 2 (ATF2), cyclic AMP response element-binding protein, and c-Jun, and increased AP-1-dependent transcription. Inhibition of Wnt secretion using the porcupine inhibitors IWP-2 and Wnt-C59 blocked neuronal differentiation, while activation or inhibition of Wnt/β-catenin signaling had no effect. Neuronal differentiation increased expression of several Wnt genes, including WNT3A, silencing of which reduced differentiation. Addition of recombinant Wnt-3a to cells treated with IWP-2 or Wnt-C59 increased AP-1 levels and restored neuronal differentiation. The effects of Wnt-3a could not be blocked by addition of Dkk-1 or IWR-1, suggesting the involvement of noncanonical signaling. Consistent with this, restoration of neuronal differentiation by Wnt-3a was reduced by inhibition of Jun N-terminal kinase (JNK) and by gene silencing of ATF2. Together, these observations suggest that β-catenin-independent Wnt signals promote neural stem/progenitor cell differentiation in a signaling pathway involving Wnt-3a, JNK, and ATF2.
AU  - Bengoa-Vergniory,N
AU  - Gorrono-Etxebarria,I
AU  - Gonzalez-Salazar,I
AU  - Kypta,RM
DO  - 10.1002/stem.1807
EP  - 3208
PY  - 2014///
SN  - 1549-4918
SP  - 3196
TI  - A switch from canonical to noncanonical Wnt signaling mediates early differentiation of human neural stem cells
T2  - Stem Cells
UR  - http://dx.doi.org/10.1002/stem.1807
UR  - http://hdl.handle.net/10044/1/25901
VL  - 32
ER  -
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