Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner
Neural crest progenitors are specified through the modulation of several signaling pathways, among which the activation of Wnt/β-catenin signaling by Wnt8 is especially critical. Glycoproteins of the Dickkopf (Dkk) family are important modulators of Wnt signaling acting primarily as Wnt antagonists....
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doaj-0e003291abef491b8034016356a95ba22021-05-05T16:02:15ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.34404Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent mannerArun Devotta0Chang-Soo Hong1Jean-Pierre Saint-Jeannet2https://orcid.org/0000-0003-3259-2103Department of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, United StatesDepartment of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, United States; Department of Biological Sciences, Daegu University, Gyeongsan, Republic of KoreaDepartment of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, United StatesNeural crest progenitors are specified through the modulation of several signaling pathways, among which the activation of Wnt/β-catenin signaling by Wnt8 is especially critical. Glycoproteins of the Dickkopf (Dkk) family are important modulators of Wnt signaling acting primarily as Wnt antagonists. Here we report that Dkk2 is required for neural crest specification functioning as a positive regulator of Wnt/β-catenin signaling. Dkk2 depletion in Xenopus embryos causes a loss of neural crest progenitors, a phenotype that is rescued by expression of Lrp6 or β-catenin. Dkk2 overexpression expands the neural crest territory in a pattern reminiscent of Wnt8, Lrp6 and β-catenin gain-of-function phenotypes. Mechanistically, we show that Dkk2 mediates its neural crest-inducing activity through Lrp6 and β-catenin, however unlike Wnt8, in a GSK3β independent manner. These findings suggest that Wnt8 and Dkk2 converge on β-catenin using distinct transduction pathways both independently required to activate Wnt/β-catenin signaling and induce neural crest cells.https://elifesciences.org/articles/34404neural crestWntDkkXenopus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arun Devotta Chang-Soo Hong Jean-Pierre Saint-Jeannet |
spellingShingle |
Arun Devotta Chang-Soo Hong Jean-Pierre Saint-Jeannet Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner eLife neural crest Wnt Dkk Xenopus |
author_facet |
Arun Devotta Chang-Soo Hong Jean-Pierre Saint-Jeannet |
author_sort |
Arun Devotta |
title |
Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner |
title_short |
Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner |
title_full |
Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner |
title_fullStr |
Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner |
title_full_unstemmed |
Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner |
title_sort |
dkk2 promotes neural crest specification by activating wnt/β-catenin signaling in a gsk3β independent manner |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-07-01 |
description |
Neural crest progenitors are specified through the modulation of several signaling pathways, among which the activation of Wnt/β-catenin signaling by Wnt8 is especially critical. Glycoproteins of the Dickkopf (Dkk) family are important modulators of Wnt signaling acting primarily as Wnt antagonists. Here we report that Dkk2 is required for neural crest specification functioning as a positive regulator of Wnt/β-catenin signaling. Dkk2 depletion in Xenopus embryos causes a loss of neural crest progenitors, a phenotype that is rescued by expression of Lrp6 or β-catenin. Dkk2 overexpression expands the neural crest territory in a pattern reminiscent of Wnt8, Lrp6 and β-catenin gain-of-function phenotypes. Mechanistically, we show that Dkk2 mediates its neural crest-inducing activity through Lrp6 and β-catenin, however unlike Wnt8, in a GSK3β independent manner. These findings suggest that Wnt8 and Dkk2 converge on β-catenin using distinct transduction pathways both independently required to activate Wnt/β-catenin signaling and induce neural crest cells. |
topic |
neural crest Wnt Dkk Xenopus |
url |
https://elifesciences.org/articles/34404 |
work_keys_str_mv |
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