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Specifying and protecting germ cell fate

Nature Reviews Molecular Cell Biology volume 16, pages 406–416 (2015)Cite this article

Subjects

Key Points

  • Germ cells generate an organism's gametes and progeny. To accomplish this, germ cells must be properly specified and protected during development.

  • In some animals, specification of the germline is continuous and involves the segregation of cytoplasmic 'determinants' during embryogenesis (preformation). In other animals, the germline is newly formed and requires inductive signalling during embryogenesis (induction).

  • Among the diverse mechanisms of germ cell specification are: transmission of maternally supplied germ plasm containing germ granules to primordial germ cells (PGCs); transmission of epigenetic memory from parent germ cells to PGCs in progeny; and expression of transcription factors that programme embryonic cells to develop as PGCs.

  • Aberrant gene expression or misguided PGC migration can cause germ cells to exhibit somatic features and even contribute to somatic tissues. In the gonad, germ cells are prevented from expressing genes that would threaten germline health and development.

  • The mechanisms that suppress aberrant gene expression and protect germline fate include global transcriptional repression in PGCs, maintenance of a germline chromatin state and translation of only germline-appropriate transcripts in germ cells.

Abstract

Germ cells are the special cells in the body that undergo meiosis to generate gametes and subsequently entire new organisms after fertilization, a process that continues generation after generation. Recent studies have expanded our understanding of the factors and mechanisms that specify germ cell fate, including the partitioning of maternally supplied 'germ plasm', inheritance of epigenetic memory and expression of transcription factors crucial for primordial germ cell (PGC) development. Even after PGCs are specified, germline fate is labile and thus requires protective mechanisms, such as global transcriptional repression, chromatin state alteration and translation of only germline-appropriate transcripts. Findings from diverse species continue to provide insights into the shared and divergent needs of these special reproductive cells.

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Figure 1: Findings that support or challenge the notion that germ granules are 'determinants' of PGC fate.
Figure 2: Chromatin regulation in the PGCs of mice and C. elegans.
Figure 3: Diverse factors and mechanisms that repress expression of somatic genes and protect germ cells from reprogramming towards somatic cells.
Figure 4: Conditions that cause adult germ cells to reprogramme towards somatic cells in C. elegans.

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Acknowledgements

The authors thank Amander Clark and anonymous reviewers for helpful discussion and comments on this review.

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Authors and Affiliations

  1. Molecular, Cell & Developmental Biology, University of California Santa Cruz, Santa Cruz, 95064, California, USA

    Susan Strome

  2. Kathryn W. Davis Center for Regenerative Biology & Medicine, Mount Desert Island Biological Laboratory, Bar Harbor, 04672, Maine, USA

    Dustin Updike

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  1. Susan Strome
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Correspondence to Susan Strome.

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PowerPoint slides

Glossary

Primordial germ cells

(PGCs). The nascent germ cells formed during embryogenesis, which ultimately generate oocytes and/or sperm in adults.

Blastomere

A type of cell that is produced by cleavage divisions during early embryogenesis.

Genital ridge

A ridge of embryonic mesoblast cells that envelopes primordial germ cells in vertebrates and develops into the sex organs.

Tudor-domain proteins

Proteins containing a conserved structural motif that binds symmetrically dimethylated Arg. This domain was originally characterized in the Drosophila melanogaster protein Tudor.

Argonaute proteins

Proteins that contain a PAZ and a PIWI domain and that bind different classes of small RNAs (for example, small interfering RNAs, micro RNAs and PIWI-interacting RNAs), which guide the Argonaute proteins to their specific target mRNAs.

Ground state

A cellular condition that is liberated from epigenetic and developmental constraints, like that found in pluripotent epiblasts.

Open chromatin

Non-compacted euchromatin that is accessible to transcriptional machinery and for gene expression.

CRISPR-based genome editing

A gene-editing technique that is derived from the bacterial immune system and is widely used to create deletions, insertions and modifications of targeted genome sequences. Since 2013, this technique has been used for genome editing in a wide range of different organisms.

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Strome, S., Updike, D. Specifying and protecting germ cell fate. Nat Rev Mol Cell Biol 16, 406–416 (2015). https://doi.org/10.1038/nrm4009

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