|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
|
Fig. 4. Wnt11-LRP6 signaling regulates axin levels in the early embryo.
(A) Western blot of embryos derived from wild-type and LRP6-depleted
oocytes (LRP6-) that were frozen at the 8-cell (stage 4) and early
blastula (stage 7) stages and probed with an affinity purified axin polyclonal
antibody. Blots were stripped and re-probed for ß-catenin, and
-tubulin antibody was used as a loading control. Axin levels were
increased in LRP6-depleted embryos (arrow; increased by 47% compared with
control). ß-catenin levels were decreased by LRP6 depletion (arrowhead;
decreased by 17% compared with controls). (B) Western blot of embryos
derived from wild-type and Wnt11-depleted oocytes (Wnt11-) that
were frozen at stage 4 and probed with an affinity purified axin polyclonal
antibody. Blots were stripped and re-probed for ß-catenin. Axin levels
were increased (arrow; 46% compared to control) in Wnt11-depleted embryos and
ß-catenin levels were decreased (arrowhead; 23% compared with control).
(C) A model of LRP6 function in the axis-forming pathway. (Ci)
Sperm activates the cortical rotation movements of the first cell cycle,
leading to a dorsal asymmetry of Wnt11 mRNA and protein, which causes
increased Wnt11 signaling dorsally (purple arrows). (Cii) By the 8-cell
stage, Wnt11 protein is secreted, mostly by dorsal vegetal cells, and binds to
LRP6. Signaling is shown between a dorsal vegetal and animal cell, although
LRP6 is likely to be present in both cells, and autocrine signaling may occur.
In LRP6-depleted embryos, Wnt11 molecules are secreted dorsally but are unable
to activate the pathway. (Ciii) An enlargement of the animal cells
shown in Fig. 3Cii at the
8-cell stage. Association of Wnt11 with the extracellular domain of LRP6
causes the degradation of axin. ß-catenin enters nuclei and binds to
Xenopus Tcf3 on the dorsal side. In LRP6-depleted embryos, Wnt11 molecules do
not bind LRP6, so axin increases in concentration and ß-catenin is
degraded to the same extent on dorsal and ventral sides, and does not enter
nuclei.
|
