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Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid.

Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid.

Authors :
Verani, R.
Cappuccio, I.
Spinsanti, P.
Gradini, R.
Caruso, A.
Magnotti, M. C.
Motolese, M.
Nicoletti, F.
Melchiorri, D.
Source :
Journal of Neurochemistry; Jan2007, Vol. 100 Issue 1, p242-250, 9p, 2 Color Photographs, 6 Black and White Photographs
Publication Year :
2007

Abstract

Cultured mouse D3 embryonic stem (ES) cells differentiating into embryoid bodies (EBs) expressed several Wnt isoforms, nearly all isotypes of the Wnt receptor Frizzled and the Wnt/Dickkopf (Dkk) co-receptor low-density lipoprotein receptor-related protein (LRP) type 5. A 4-day treatment with retinoic acid (RA), which promoted neural differentiation of EBs, substantially increased the expression of the Wnt antagonist Dkk-1, and induced the synthesis of the Wnt/Dkk-1 co-receptor LRP6. Recombinant Dkk-1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and distal-less homeobox gene (Dlx-2). Recombinant Dkk-1 was able to inhibit the Wnt pathway, as shown by a reduction in nuclear β-catenin levels. Remarkably, the antisense- or small interfering RNA-induced knockdown of Dkk-1 largely reduced the expression of Dlx-2, and the neuronal marker β-III tubulin in EBs exposed to RA. These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00223042
Volume :
100
Issue :
1
Database :
Complementary Index
Journal :
Journal of Neurochemistry
Publication Type :
Academic Journal
Accession number :
23634314
Full Text :
https://doi.org/10.1111/j.1471-4159.2006.04207.x