Esrrb function is required for proper primordial germ cell development in presomite stage mouse embryos

Area of Science:

• Developmental biology
• Molecular endocrinology
• Genetics

Background:

• Estrogen related receptor beta (Esrrb) is crucial for embryonic stem cell pluripotency.
• In early mouse embryos, Esrrb is specifically expressed in the extraembryonic ectoderm (ExE) and vital for trophoblast development.
• Esrrb maintains trophoblast stem (TS) cells in vitro.

Purpose of the Study:

• To identify in vivo regulatory targets of Esrrb in the post-implantation mouse embryo.
• To elucidate the role of Esrrb in regulating Bmp4 expression and primordial germ cell (PGC) development.

Main Methods:

• Microarray analysis of Esrrb-null versus wild-type ExE.
• Esrrb ChIP-seq and luciferase reporter assays in TS cells.
• CRISPR/Cas9-mediated deletion of a Bmp4 enhancer region in mice.

Main Results:

• Identified 30 genes down-regulated in Esrrb-mutant ExE, including Bmp4.
• Esrrb binds to an enhancer region of the Bmp4 locus.
• Esrrb-null and enhancer knockout embryos showed reduced Bmp4 expression and fewer PGCs.

Conclusions:

• Esrrb acts as an upstream regulator of Bmp4 in the ExE.
• Esrrb signaling is essential for proper PGC development in mice.