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#dominant negative

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frog development

Expression of a dominant negative GSK3 in dorsal cells results in:

Dominant-negative GSK3 expressed in dorsal marginal zone further inhibits already partially suppressed GSK3 activity dorsally, leading to even greater beta-catenin stabilization and hyperdorsal phenotype. Extra beta-catenin expands organizer gene domains chordin and goosecoid laterally, converting paraxial and lateral mesoderm into axial notochord and somitic tissue, enlarging neural plate while reducing ventral blood islands and epidermis. This contrasts ventralization seen with constitutively active GSK3. Result is dorsalized embryo with radial neuralization and exaggerated dorsal structures due to enhanced Wnt signaling. This illustrates conserved developmental logic of morphogen gradients patterning embryonic axes through Wnt and BMP antagonism.

Ref: Heasman, Wnt signaling in Xenopus patterning, Development Journal, GSK3 mutant phenotypes.

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frog development

Dominant negative GSK3 expression in ventral cells results in:

Glycogen synthase kinase-3 normally phosphorylates beta-catenin at N-terminal residues targeting it for beta-TrCP mediated ubiquitination in ventral cells. Dominant-negative GSK3 carries mutation abolishing kinase activity but retains binding to Axin complex, competitively blocking endogenous enzyme. When expressed on ventral side, it allows beta-catenin stabilization, nuclear entry, activation of Siamois and Twin and formation of ectopic Nieuwkoop center. Ectopic center induces secondary Spemann organizer ventrally that organizes host tissues into complete secondary embryonic axis with independent notochord and neural structures. This illustrates conserved developmental logic of morphogen gradients patterning embryonic axes through Wnt and BMP antagonism.

Ref: Heasman et al., Wnt signaling and GSK3 in Xenopus axis, Development Journal, Axis duplication mechanism.

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