期刊
DEVELOPMENT
卷 134, 期 23, 页码 4255-4263出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.005942
关键词
Dkk; Kremen; LRP6; Mesd; slug; sox10; Wnt; xenopus
资金
- Medical Research Council [G117/506] Funding Source: researchfish
- MRC [G117/506] Funding Source: UKRI
- Medical Research Council [G117/506] Funding Source: Medline
Kremen 1 and 2 (Krm1/2) are transmembrane receptors for Wnt antagonists of the Dickkopf (Dkk) family and function by inhibiting the Wnt co-receptors LRP5/6. Here we show that Krm2 functions independently from Dkks during neural crest (NC) induction in Xenopus. Krm2 is co-expressed with, and regulated by, canonical Wnts. Krm2 is differentially expressed in the NC, and morpholino-mediated Krm2 knockdown inhibits NC induction, which is mimicked by LRP6 depletion. Conversely, krm2 overexpression induces ectopic NC. Kremens bind to LRP6, promote its cell-surface localization and stimulate LRP6 signaling. Furthermore, Krm2 knockdown specifically reduces LRP6 protein levels in NC explants. The results indicate that in the absence of Dkks, Kremens activate Wnt/beta-catenin signaling through LRP6.
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