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.
| Original language | English |
|---|---|
| Pages (from-to) | 242-250 |
| Number of pages | 9 |
| Journal | Journal of Neurochemistry |
| Volume | 100 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2007 |
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Keywords
- Cell cultures
- Dickkopf1
- Embryonic stem cells
- Neural differentiation
- Retinoic acid
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
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. / Verani, R.; Cappuccio, I.; Spinsanti, P.; Gradini, R.; Caruso, A.; Magnotti, M. C.; Motolese, M.; Nicoletti, F.; Melchiorri, D.
In: Journal of Neurochemistry, Vol. 100, No. 1, 01.2007, p. 242-250.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Verani, R.
AU - Cappuccio, I.
AU - Spinsanti, P.
AU - Gradini, R.
AU - Caruso, A.
AU - Magnotti, M. C.
AU - Motolese, M.
AU - Nicoletti, F.
AU - Melchiorri, D.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Cell cultures
KW - Dickkopf1
KW - Embryonic stem cells
KW - Neural differentiation
KW - Retinoic acid
UR - http://www.scopus.com/inward/record.url?scp=33846172711&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846172711&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.04207.x
DO - 10.1111/j.1471-4159.2006.04207.x
M3 - Article
C2 - 17064353
AN - SCOPUS:33846172711
VL - 100
SP - 242
EP - 250
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 1
ER -