Of Mice and Men: In Vivo and In Vitro Studies of Primordial Germ Cell Specification

Abstract

Specification of mouse primordial germ cells (PGCs), the precursors of sperm and eggs, involves three major molecular events: repression of the somatic program; re-acquisition of pluripotency; and reprogramming to a unique epigenetic ground state. Gene knockout studies in mouse models, along with global transcriptome analyses, have revealed the key signaling pathways and transcription factors essential for PGC specification. Knowledge obtained from these studies has been utilized extensively to develop robust in vitro PGC induction models not only in mice but also in humans. These models have, in turn, formed the basis for a detailed understanding of the signaling pathways and epigenetic dynamics during in vivo PGC specification and development. Recapitulation of human PGC specification in culture is of tremendous significance for understanding the mechanisms of human germ cell development in normal and disease states and has implications for addressing germ-cell-based causes of infertility.

Transgenerational Epigenetic DNA Methylation Editing and Human Disease

“…In mice, PGCs emerge from the proximal epiblast, numbering approximately 40 by 7.25 days post coitum (dpc) [65]. Migration across the posterior primitive streak to embryonic endoderm follows, with eventual migration to the genital ridge and gonad at 10 dpc [65,66]. It is during the migration and colonization of the genital ridges when global erasure of DNAme occurs, from ~70% to 4% at 13.5 dpc PGCs [15,66,67].…”

Germ Granules in Animal Oogenesis

“…That means that cell fate is defined not by the deposited maternal components, but rather it is induced by signaling events from the surrounding cells during embryo development. The inductive mechanism is attributed to all mammals, including mice and humans [ 44 , 45 ]. The switch between the two mechanisms occurred many times during evolution.…”

Primordial Germ Cell Specification in Vertebrate Embryos: Phylogenetic Distribution and Conserved Molecular Features of Preformation and Induction

“…Induction has been proposed to be the ancestral mode of PGC specification, largely due to the presence of preformation in multiple derived lineages (presumably through convergent evolution) whereas induction is often associated with basal phylogenetic branches ( Johnson et al, 2003a ; Ewen-Campen et al, 2013 ; Figure 4 ). In general, the inductive mode of PGC specification requires the coordination of several zygotically driven processes in PGC precursors: repression of somatic fate, activation of germline-associated and pluripotency genes, and epigenetic reprogramming ( Kumar and DeFalco, 2017 ).…”