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#Disheveled

4 public questions tagged with this topic.

Sea Urchin -ll

Disheveled prevents degradation of:

Disheveled (Dsh) is key intracellular transducer of Wnt signaling vegetally localized in sea urchin egg cortex during oogenesis. It binds and inhibits Axin-GSK-3β-APC destruction complex responsible for phosphorylating β-catenin at N-terminus and marking it for ubiquitin-proteasome degradation. By preventing phosphorylation, Disheveled stabilizes β-catenin allowing cytoplasmic accumulation and subsequent nuclear import in vegetal blastomeres. Nuclear β-catenin partners with TCF/LEF to activate endomesodermal gene regulatory network and Pmar1. Hence Disheveled action preserves β-catenin, establishing vegetal polarity and micromere specification early in embryogenesis before zygotic transcription.

Ref: Weitzel et al., Development 2004, Disheveled localization; Gilbert Chapter 8: Wnt/β-catenin regulation by Dsh.

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Sea urchin -lll

Disheveled protein in sea urchin embryos is localized initially in:

Dishevelled protein acts as key adaptor upstream of beta-catenin in Wnt pathway hierarchy. In sea urchin oocytes before fertilization, Dishevelled protein and mRNA are anchored to vegetal cortex via interactions with actin-associated proteins, cortically localized vesicles, and cytoskeletal scaffolds. This pre-fertilization localization establishes asymmetry inherited by micromeres after fourth unequal cleavage. Vegetal cortical Dishevelled locally inhibits GSK-three, permitting beta-catenin accumulation vegetally and activating endomesoderm genes. If Dishevelled were localized animally or in blastocoel, vegetal specification would fail, animalizing embryo and altering endomesoderm patterning strongly.

Ref: Davidson, Sea Urchin GRN, Chapter: Dishevelled localized in vegetal cortex before fertilization.

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frog development

Translocation of Disheveled and Wnt11 occurs to:

Early after fertilization vegetal cortical region contains Wnt11 mRNA and Dishevelled protein anchored to cortex. Microtubule polymerization between sperm aster and vegetal cortex enables plus-end directed transport of these determinants via kinesin toward future dorsal side during 30-degree cortical rotation. Imaging with Dsh-GFP demonstrates accumulation in dorsal marginal zone preceding beta-catenin nuclear entry. Translocation to ventral side would induce ectopic axis, to animal hemisphere or vegetal pole alone insufficient. Normal pattern to dorsal side establishes Nieuwkoop center and dorso-ventral polarity. This illustrates conserved developmental logic of morphogen gradients patterning embryonic axes through Wnt and BMP antagonism.

Ref: Weaver and Kimelman, Wnt11 and Disheveled transport during cortical rotation, Development Journal, Axis establishment.

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