Lessons for inductive germline determination

Abstract

SUMMARY Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates—two of the milestones of reproduction and development—in which animals use contrasting strategies to activate similar pathways.

Kinesin-1 interacts with Bucky ball to form germ cells and is required to pattern the zebrafish body axis

“…A Kif5Ba-Buc interaction required for germ plasm assembly and germline specification Although germline development in all animals relies on conserved genetic factors, two main modes of germline specification exist (Ewen-Campen et al, 2010;Lesch and Page, 2012;Seervai and Wessel, 2013). Germline stem cells are either induced by zygotic factors or rely on the inheritance of maternal GP to specify PGCs (Dosch, 2014;Marlow, 2010).…”

“…In sexually reproducing animals, primordial germ cells (PGCs), germline stem cells that form the gametes, are specified early in development via induction by zygotic factors or inheritance of maternally deposited RNAs and proteins, termed germ plasm (GP) Lesch and Page, 2012;Seervai and Wessel, 2013). Although key regulators of germline development are conserved, maternal inheritance modes utilize diverse regulators (e.g.…”

“…Although key regulators of germline development are conserved, maternal inheritance modes utilize diverse regulators (e.g. oskar in insects and buc in vertebrates) and mechanisms of GP assembly Lesch and Page, 2012;Seervai and Wessel, 2013). GP is both necessary and sufficient for germline specification (Hashimoto et al, 2004;Hathaway and Selman, 1961;Illmensee and Mahowald, 1974;Togashi et al, 1986), yet it remains mysterious how this process is regulated.…”

Sex Reversal in Amphibians

“…The germ plasm will be partitioned asymmetrically during cleavage and will be concentrated in the cells located at the vegetal pole that become primordial germ cells (PGCs) and have an endodermal origin. This mechanism called preformation is also known in Drosophila or Caenorhabditis for instance [Seervai and Wessel, 2013].…”

Global transcriptional repression: An initial and essential step for Plasmodium sexual development

“…In mammals, germ-line formation occurs in the early embryo when a small number of PGCs is specified among embryonic cells with a somatic fate (16). This type of determination of the germ line, referred to as inductive determination, is thought to be the most ancient mechanism for germ-line formation in animals (17). The gametocytogenesis of Plasmodium parasites appears to be of this type, because only a small number of blood-stage parasites, most of which repeatedly enter an asexual proliferation cycle, will become gametocytes.…”