Abstract
A critical step in animal development is the specification of primordial germ cells (PGCs), the precursors of the germline. Two seemingly mutually exclusive mechanisms are implemented across the animal kingdom: epigenesis and preformation. In epigenesis, PGC specification is non-autonomous and depends on extrinsic signaling pathways. The BMP pathway provides the key PGC specification signals in mammals. Preformation is autonomous and mediated by determinants localized within PGCs. In Drosophila, a classic example of preformation, constituents of the germ plasm localized at the embryonic posterior are thought to be both necessary and sufficient for proper determination of PGCs. Contrary to this longstanding model, here we show that these localized determinants are insufficient by themselves to direct PGC specification in blastoderm stage embryos. Instead, we find that the BMP signaling pathway is required at multiple steps during the specification process and functions in conjunction with components of the germ plasm to orchestrate PGC fate.
Highlights
Sexual reproduction enables multicellular organisms to transmit genetic information from one generation to the
Proper specification of primordial germ cells (PGCs) is crucial as PGCs serve as the precursors of germline stem cells
Our data on the BMP signaling pathway challenge this long-held view of PGC specification and suggest that appropriate specification of embryonic PGCs is sensitive to the BMP ligand, decapentaplegic, and its cognate receptor, thickveins
Summary
Sexual reproduction enables multicellular organisms to transmit genetic information from one generation to the next. The GSCs of sexually mature animals do not arise de novo. Rather, they are derived from a special group of cells, the primordial germ cells (PGCs), that are set aside from the remaining somatic cells during a very early phase of embryonic development. One of the key PGC specification steps in most animals is the downregulation of transcription. In mammals, progenitors of the cells that give rise to the germline undergo zygotic genome activation (ZGA) like other cells in the embryo; after the initial steps in PGC specification, transcription of somatic genes is largely terminated, and these cells begin to revert to an earlier, pluripotent state [6,7,8]. The cell lineage that produces the germline is set aside at the first division, and, when transcription commences in the remaining somatic cells at the 3–4 cell stage, it remains transcriptionally quiescent, as do the daughter cells in the lineage destined to become germline [9, 10]
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