Xenopus skip modulates Wnt/beta-catenin signaling and functions in neural crest induction

Area of Science:

• Molecular Biology
• Developmental Biology
• Gene Regulation

Background:

• Canonical Wnt signaling, mediated by the beta-catenin-LEF complex, controls gene transcription.
• Numerous cofactors are essential for beta-catenin-LEF complex function.
• The splicing factor SKIP (SNW/NcoA62) is a conserved transcriptional co-regulator.

Purpose of the Study:

• To investigate the role of SKIP in canonical Wnt signaling.
• To determine if SKIP interacts with components of the beta-catenin-LEF complex.
• To elucidate SKIP's function in Wnt target gene regulation.

Main Methods:

• Formation of a ternary complex involving SKIP, LEF1, and HDAC1 was analyzed.
• Loss-of-function studies were performed to assess SKIP's necessity for Wnt signaling.
• The impact of SKIP on beta-catenin stability and Wnt signaling was examined.
• Xenopus embryo models were used to study SKIP's role in neural crest induction.

Main Results:

• SKIP forms a ternary complex with LEF1 and HDAC1, mediating target gene repression.
• SKIP is essential for Wnt signaling-induced target gene transactivation.
• C-terminally truncated SKIP stabilizes beta-catenin and enhances Wnt signaling.
• Both SKIP overexpression and knockdown in Xenopus embryos reduce neural crest induction.

Conclusions:

• SKIP is a novel component of the beta-catenin transcriptional complex.
• SKIP plays a critical role in canonical Wnt signaling pathway.
• SKIP's function is crucial for developmental processes like neural crest induction.