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First published online 31 October 2007
doi: 10.1242/dev.005942

Development 134, 4255-4263 (2007)
Published by The Company of Biologists 2007
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Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling

Christine Hassler1, Cristina-Maria Cruciat1, Ya-Lin Huang1, Sei Kuriyama2, Roberto Mayor2 and Christof Niehrs1,*

1 Department of Molecular Embryology, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
2 Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

* Author for correspondence (e-mail: niehrs{at}dkfz-heidelberg.de)

Accepted 4 September 2007

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/ß-catenin signaling through LRP6.

Key words: Dkk, Kremen, LRP6, Mesd, Slug, Sox10, Wnt, Xenopus




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