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Committing the primordial germ cell: An updated molecular perspective

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The germ line is a crucial cell lineage that is distinct from somatic cells, and solely responsible for the trans‐generational transmission of hereditary information in metazoan sexual reproduction. Primordial germ cells (PGCs)—the precursors to functional germ cells—are among the first cell types to be allocated in embryonic development, and this lineage commitment is a critical event in partitioning germ line and somatic tissues. Classically, mammalian PGC development has been largely informed by investigations on mouse embryos and embryonic stem cells. Recent findings from corresponding nonrodent systems, however, have indicated that murine PGC specification may not be fully archetypal. In this review, we outline the current understanding of molecular mechanisms in PGC specification, emphasizing key transcriptional events, and focus on salient differences between early human and mouse PGC commitment. Beyond these latest findings, we also contemplate the future outlook of inquiries in this field, highlighting the importance of comprehensively understanding early fate decisions that underlie the segregation of this unique lineage.

This article is categorized under:

  • Developmental Biology > Stem Cell Biology and Regeneration
  • Biological Mechanisms > Cell Fates
  • Physiology > Mammalian Physiology in Health and Disease
Anatomical observations of embryonic PGCs. (a) Schematic diagram of the peri‐gastrulation mouse embryo, indicating nascent mPGCs observed in the posterior embryo. (b) Schematic diagram of the mouse embryo at about E9.5, showing migratory, committed mPGCs colonizing the genital ridge. (c) Schematic diagram of the week 3 human embryo, with the earliest observed hPGCs in the yolk sac wall. (d) Schematic diagram of the week 5 to 6 human embryo, indicating migratory hPGCs populating the genital ridge. Diagrams are not to scale. ExE; extraembryonic ectoderm. PGC; primordial germ cell
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Current outlook of human PGC specification. Combined in vitro and in vivo findings have uncovered a hPGC specification mechanism distinct from that of the mouse. This flowchart includes the main, best‐characterized factors in pro‐hPGC pathways; factors in red are the key elements that differ between mPGC and hPGC development. Of note, SOX17 lies upstream of PRDM1 in the PGC specification circuitry, and the roles of PRDM14 and NANOG in specifying hPGCs are unclear. Additionally, EOMES has yet to be characterized as a molecular player in mPGC commitment, while SOX2 is not expressed in committed hPGCs. PGC; primordial germ cell
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A molecular paradigm for mouse PGC specification. (a) In the peri‐gastrulation/implantation mouse embryo, BMP and WNT signals emanate from the posterior ExE, visceral endoderm, and the proximal epiblast itself, impinging and acting on the posterior proximal epiblast. These signals represent competence and inductive modalities to drive receptive epiblast cells towards germ lineage fate. (b) a wealth of in vivo and in vitro data has unveiled the molecular pathways and players through which the mPGC lineage is specified. This flowchart demonstrates the major factors involved. ExE; extraembryonic ectoderm. PGC; primordial germ cell
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Developmental Biology > Stem Cell Biology and Regeneration
Biological Mechanisms > Cell Fates
Physiology > Mammalian Physiology in Health and Disease

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