Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling.
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.
Hassler
Christine
C
Department of Molecular Embryology, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Cruciat
Cristina-Maria
CM
Huang
Ya-Lin
YL
Kuriyama
Sei
S
Mayor
Roberto
R
Niehrs
Christof
C
D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008156:Luciferases / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D011973:Receptors, LDL / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008565:Membrane Proteins; D011973:Receptors, LDL; D051153:Wnt Proteins; D029867:Xenopus Proteins; C471148:kremen1 protein, Xenopus; C471149:kremen2 protein, Xenopus; D008156:Luciferases