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

Okamura, Eiichi, Tam, Oliver H, Posfai, Eszter, Li, Lingyu, Cockburn, Katie, Lee, Cheryl QE, Garner, Jodi, Rossant, Janet (November 2019) Esrrb function is required for proper primordial germ cell development in presomite stage mouse embryos. Developmental Biology, 455 (2). pp. 382-392. ISSN 0012-1606

PDF 1-s2.0-S0012160619300867-main.pdf - Published Version Download (3MB)

Abstract

Estrogen related receptor beta (Esrrb) is an orphan nuclear receptor that is required for self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in the early post-implantation mouse embryo, Esrrb is specifically expressed in the extraembryonic ectoderm (ExE) and plays a crucial role in trophoblast development. Previous studies showed that Esrrb is also required to maintain trophoblast stem (TS) cells, the in vitro stem cell model of the early trophoblast lineage. In order to identify regulatory targets of Esrrb in vivo, we performed microarray analysis of Esrrb-null versus wild-type post-implantation ExE, and identified 30 genes down-regulated in Esrrb-mutants. Among them is Bmp4, which is produced by the ExE and known to be critical for primordial germ cell (PGC) specification in vivo. We further identified an enhancer region bound by Esrrb at the Bmp4 locus by performing Esrrb ChIP-seq and luciferase reporter assay using TS cells. Finally, we established a knockout mouse line in which the enhancer region was deleted using CRISPR/Cas9 technology. Both Esrrb-null embryos and enhancer knockout embryos expressed lower levels of Bmp4 in the ExE, and had reduced numbers of PGCs. These results suggested that Esrrb functions as an upstream factor of Bmp4 in the ExE, regulating proper PGC development in mice.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > small molecules > estrogen organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent bioinformatics > genomics and proteomics > small molecules
CSHL Authors:	Tam, Oliver H.
Communities:	CSHL labs > Hammell M. lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 November 2019
Date Deposited:	03 Feb 2021 16:38
Last Modified:	02 Feb 2024 19:42
URI:	https://repository.cshl.edu/id/eprint/39809

Actions (login required)

Administrator's edit/view item