Analysis of Dishevelled signalling pathways during Xenopus development

¹Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA. ssokol@bidmc.harvard.edu

|November 1, 1996

Summary

Dishevelled (Dsh) protein is crucial for vertebrate development, acting upstream of beta-catenin in Wnt signaling. This study reveals the PDZ domain

Area of Science:

Background:

Wnt, Frizzled, and Notch proteins are key regulators of embryonic development across species.
Dishevelled (Dsh) protein mediates cellular responses to Wingless, Notch, and Frizzled signals.
The precise molecular function of Dsh in vertebrate development remains incompletely understood.

Purpose of the Study:

To elucidate the role of endogenous Xenopus Dsh (Xdsh) in early vertebrate development.
To investigate the function of Xdsh in Wnt and Dsh signaling pathways.
To clarify the necessity of the PDZ domain for Xdsh signal transduction.

Main Methods:

Construction and expression of a dominant-negative mutant of Xenopus Dsh (Xdd1) lacking the PDZ/DHR domain.
Injection of Xdd1 mRNA into Xenopus embryos to assess its effects on axis formation and morphogenetic movements.
Analysis of Xdd1's impact on mesoderm induction and differentiation in response to signaling factors.

Main Results:

Overexpression of Xdd1 inhibited secondary axis induction by wild-type Xdsh and Xwnt8, but not by beta-catenin.
Dorsal Xdd1 expression led to posterior truncations, a phenotype suppressed by wild-type Xdsh.
Xdd1 disrupted convergent extension movements without affecting mesoderm induction or differentiation.

Conclusions:

Vertebrate Dsh is essential for Wnt signal transduction, functioning upstream of beta-catenin.
The PDZ domain is critical for Xdsh-mediated signal transduction.
Endogenous Xdsh plays a vital role in regulating embryonic morphogenetic movements.

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