The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Vertebrate segmentation relies on the segmentation clock, a molecular oscillator controlling somite formation.
• Cyclic expression of Notch signaling genes exemplifies the segmentation clock.
• Wnt3a influences the spatiotemporal expression of cyclic Notch genes, but the mechanism is unclear.

Purpose of the Study:

• To elucidate the mechanism by which Wnt3a controls cyclic Notch gene expression.
• To identify the role of Mesogenin1 (Msgn1) in the Wnt3a-mediated segmentation clock pathway.

Main Methods:

• Transcriptional profiling of Wnt3a (-/-) embryos.
• Genome-wide studies of Msgn1 activity in embryonic stem cells.

Main Results:

• Mesogenin1 (Msgn1), a bHLH transcription factor, is identified as a direct Wnt3a target gene.
• Msgn1 acts as a major transcriptional activator of Notch signaling.
• Msgn1 synergizes with Notch to induce clock gene expression and indirectly regulates Fgf and Wnt pathway genes.

Conclusions:

• Msgn1 is a central component in the transcriptional cascade translating spatial Wnt3a gradients into temporal clock gene patterns.
• This study reveals Msgn1 as a critical link between Wnt3a and the segmentation clock machinery.
• Understanding this pathway is vital for comprehending vertebrate body plan development.