Wnt11/beta-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin.
Current models of canonical Wnt signaling assume that a pathway is active if beta-catenin becomes nuclearly localized and Wnt target genes are transcribed. We show that, in Xenopus, maternal LRP6 is essential in such a pathway, playing a pivotal role in causing expression of the organizer genes siamois and Xnr3, and in establishing the dorsal axis. We provide evidence that LRP6 acts by degrading axin protein during the early cleavage stage of development. In the full-grown oocyte, before maturation, we find that axin levels are also regulated by Wnt11 and LRP6. In the oocyte, Wnt11 and/or LRP6 regulates axin to maintain beta-catenin at a low level, while in the embryo, asymmetrical Wnt11/LRP6 signaling stabilizes beta-catenin and enriches it on the dorsal side. This suggests that canonical Wnt signaling may not exist in simple off or on states, but may also include a third, steady-state, modality.
Kofron
Matt
M
Division of Developmental Biology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229-3039, USA.
Birsoy
Bilge
B
Houston
Douglas
D
Tao
Qinghua
Q
Wylie
Christopher
C
Heasman
Janet
J
D000818:Animals; D060466:Axin Protein; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D005260:Female; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008954:Models, Biological; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D012333:RNA, Messenger; D011973:Receptors, LDL; D012097:Repressor Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin; C512785:wnt11b protein, Xenopus