Project description:To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/β-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation. E7.5 mouse embryos were collected. One Dullard-heterozygous embryo and one Dullard-homozygous embryo were used for the analysis.
Project description:To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/β-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation.
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.
