Dullard/Ctdnep1 modulates WNT signalling activity for the formation of primordial germ cells in the mouse embryo

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Dullard/Ctdnep1 is a serine/threonine phosphatase involved in eukaryotic RNA polymerase II C-terminal domain regulation.
• Primordial germ cell (PGC) formation in mice is regulated by BMP4 and WNT3 signaling pathways.
• Dullard's role in PGC development and its interaction with BMP and WNT pathways require clarification.

Purpose of the Study:

• To investigate the function of Dullard in primordial germ cell (PGC) formation.
• To determine Dullard's role in BMP and WNT signaling pathways during germ cell specification.
• To elucidate the molecular mechanisms by which Dullard influences PGC development.

Main Methods:

• Analysis of Dullard mutations in mouse embryos.
• Assessment of BMP4 and p-Smad activity.
• Evaluation of WNT/β-catenin signaling and Dishevelled 2 (Dvl2) levels.
• Examination of PGC numbers in wild-type, mutant, and compound heterozygous embryos.

Main Results:

• Dullard mutations did not affect BMP4 or p-Smad activity, challenging its proposed negative regulation of BMP receptors.
• Loss of Dullard function synergistically reduced PGC numbers when combined with Wnt3 deficiency.
• Dullard deficiency led to down-regulation of WNT/β-catenin signaling and reduced Dvl2 protein levels.

Conclusions:

• Dullard positively regulates WNT signaling, playing a critical role in germ cell lineage specification.
• Dullard fine-tunes WNT signaling by modulating ligand/antagonist expression and Dvl2 protein availability.
• The findings redefine Dullard's function from BMP pathway regulation to essential WNT pathway modulation in PGC development.