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XB-ART-36709
Development December 1, 2007; 134 (23): 4255-63.

Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling.

Hassler C , Cruciat CM , Huang YL , Kuriyama S , Mayor R , Niehrs C .


Abstract
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.

PubMed ID: 17978005
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acss2.2 bmp4 dkk1 gal.2 h4c4 kremen1 kremen2 lrp5 lrp6 snai2 sox10 wnt3a wnt8a
Morpholinos: kremen2 MO1 kremen2 MO2 lrp6 MO1


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