Foxj3 represses TGF-β signals-responsive transcriptions in Xenopus early development

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Forkhead box (Fox) proteins are crucial transcription factors involved in embryonic development and adult functions.
• Fox proteins possess a conserved DNA-binding domain known as the 'forkhead box'.
• Foxj3's role in regulating gene transcription requires further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms by which Foxj3 functions as a transcriptional repressor.
• To determine Foxj3's role in regulating Activin/Nodal and BMP signaling pathways in Xenopus embryos.

Main Methods:

• Gain- and loss-of-function studies using mRNA microinjection and morpholino oligos.
• Quantitative reverse transcription PCR (RT-PCR) and luciferase assays to assess gene transcription.
• Whole-mount in situ hybridization and animal cap assays to analyze embryonic development and gene expression.

Main Results:

• Foxj3 overexpression repressed Activin/Nodal and BMP4-induced gene responses, leading to developmental defects.
• Foxj3 knockdown enhanced Nodal-responsive transcription and resulted in malformed embryos.
• Foxj3-mediated repression was dependent on RNF152 and could be blocked by β-catenin.

Conclusions:

• Foxj3 functions as a transcriptional repressor in Xenopus early development.
• The RNF152/β-catenin signaling axis is essential for Foxj3's repressive function.
• Foxj3 plays a critical role in regulating TGF-β-dependent transcriptional responses.