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Mechanisms guiding primordial germ cell migration: strategies from different organisms

Key Points

  • Primordial germ cell (PGC) migration provides a useful system for studying a group of individually migrating cells in vivo.

  • PGC migration in all species follows similar steps: initiation of polarity and directed migration, regulated migration by attractive and repulsive cues, and termination of migration at the site of gonad formation.

  • PGCs frequently use G protein-coupled receptor signalling to reach their target tissues, a mechanism found in many types of migrating cells.

  • Lipids have an essential role in regulating PGC migration and seem to work both as chemoattractants themselves and by modifying and activating other chemoattractants.

  • Cell adhesion molecules, in particular cadherins, have important roles in several steps of PGC migration, such as initiation of migration, migration through somatic tissues, cessation of migration and gonad coalescence.

  • The migration of PGCs is closely linked with their survival and PGCs that do not properly migrate to the gonad are usually eliminated by cell death. However, mechanisms of PGC death might differ between species.

Abstract

The regulated migration of cells is essential for development and tissue homeostasis, and aberrant cell migration can lead to an impaired immune response and the progression of cancer. Primordial germ cells (PGCs), precursors to sperm and eggs, have to migrate across the embryo to reach somatic gonadal precursors, where they carry out their function. Studies of model organisms have revealed that, despite important differences, several features of PGC migration are conserved. PGCs require an intrinsic motility programme and external guidance cues to survive and successfully migrate. Proper guidance involves both attractive and repulsive cues and is mediated by protein and lipid signalling.

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Figure 1: Stages of primordial germ cell migration.
Figure 2: Initiation of primordial germ cell migration.
Figure 3: Molecular regulation of PGC migration paths.

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Acknowledgements

We thank members of the Lehmann laboratory for comments on the manuscript, A. Paksa, N. Peyriéras and E. Raz for the zebrafish movies and B. Dudley and K. Molyneaux for sharing the mouse movie. B. Richardson is supported by the National Institutes of Health (NIH) National Research Service Award fellowship F32HD062160. Our work on primordial germ cell migration is supported by the NIH grant RO1HD041900. R. Lehmann is a Howard Hughes Medical Institute investigator. We thank M. Starz-Gaiano for her drawings, on which the figure in box 1 is based and we thank M. Starz-Gaiano and A. Santos for allowing us to adapt their figures for figure 1.

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Correspondence to Ruth Lehmann.

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Supplementary information

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Supplementary information S1 (movie) | In vivo timelapse of primordial germ cell migration through the midgut in Drosophila melanogaster. (MOV 2708 kb)

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Supplementary information S2 (movie) | In vivo timelapse of bilateral migration of primordial germ cells into the mesoderm in Drosophila melanogaster. (MOV 2093 kb)

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Supplementary information S3 (movie) | In vivo timelapse of primordial germ cell migration in zebrafish. (MOV 9790 kb)

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Supplementary information S4 (movie) | In vivo timelapse of primordial germ cell migration in mouse. (AVI 7697 kb)

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Ruth Lehmann's homepage

Glossary

Gastrulation

A crucial step in animal development in which the layout of the embryo is dramatically restructured by cell migration to form the three germ layers: ectoderm, mesoderm and endoderm.

Primordium

An organ or tissue at its earliest stages of development.

Extraembryonic ectoderm

A cell layer in mice that lies outside of the embryo and eventually differentiates to form the chorion.

Visceral endoderm

An extraembryonic cell layer that covers the early mouse embryo and has important signalling functions during development.

Epiblast

The inner layer of the developing vertebrate embryo that gives rise to the fetus.

Posterior midgut pocket

A luminal structure in the developing D. melanogaster embryo that is formed by the midgut primordium during gastrulation.

Adherens junction

A protein complex that is found at cell–cell junctions in epithelial tissues and is composed of catenins, cadherins and actin filaments.

Primitive streak

The site of gastrulation in many vertebrates, including mice, where precursors of the mesoderm and endoderm ingress into the embryo.

Allantois

An extraembryonic membrane formed near the hindgut of mammalian embryos that is important for collecting embryonic waste and for the development of the umbilical cord and placenta.

Somite

A mesodermal structure found on either side of the neural tube in vertebrate embryos that eventually gives rise to muscle, skin and vertebrae. It is often used to stage embryos.

Genital ridge

A mesodermal precursor to the somatic gonads in vertebrate embryos (also known as the gonadal ridge).

Apoptosis

A process of programmed cell death that is characterized by DNA fragmentation and the loss of membrane integrity.

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Richardson, B., Lehmann, R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol 11, 37–49 (2010). https://doi.org/10.1038/nrm2815

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