Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Abstract

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

Single-cell epigenomic dysregulation of Systemic Sclerosis fibroblasts via CREB1/EGR1 axis in self-assembled human skin equivalents

“…Top TFs for this cluster were OVAL1 and OVAL2, which are associated with pluripotency and the specification of cell lineage (Fig. 4B , Table 1 , Table S6) (37). E2F1, which regulates the cell cycle and inflammation (38), and NFYA, which helps orchestrate monocyte differentiation, were also upregulated (39).…”

Ovo is a master regulator of the piRNA pathway in animal ovarian germ cells

“…Most vertebrates have three homologs of the fly ovo gene (e.g., mouse Ovol1 , Ovol2 , and Ovol3 ) with the Ovol2 paralog involved in the development of primordial germ cells (PGCs) 52,53 . Clustering of all vertebrate TF motifs in the JASPAR database (2,022 vertebrates CORE) revealed high similarities between the motifs of Ovo family TFs and, remarkably, A-MYB ( Figure 7a ), a testis-specific TF previously reported to control transcription of both the germline piRNA pathway genes and piRNA clusters in male mice.…”

“…Overall, our results suggest a conserved regulatory mechanism utilizing CCGTTA motifs underpinning the expression patterns of germline piRNA pathway in metazoan species, where Ovo/OVOL2 interaction with the motifs in ovaries serves as a female counterpart of the male-specific regulation by A-MYB in testes (Figure 7e). (c) OVOL2 ChIP-seq from female mouse PGCLCs (day 2 of PGCLC induction; overexpressing transgenic mouse Ovol2a; data from 52 ) showing OVOL2 binding to the CCGTTA motifs (OVOL2 motifs) within the mouse ovary-specific piRNA clusters (small RNA-seq data from 54 ). (d) Ranking of the human piRNA clusters by their expression levels in human fetal ovaries (rpkm; data from 56 ).…”

Scalable and Efficient Generation of Mouse Primordial Germ Cell-like Cells

“…PGC development entails important regulatory and epigenetic events that lay the groundwork for subsequent sex-specific gametogenesis programs. Although in vitro PGCLC induction systems have facilitated molecular studies of the specification and developmental events of the germ cell lineage 9,11,21,[33][34][35][36][37] , current techniques have shortcomings in terms of efficiency, scalability and long-term culture. Our 4TF-induction system addresses these limitations.…”