Elsevier

Current Opinion in Cell Biology

Volume 42, October 2016, Pages 128-137
Current Opinion in Cell Biology

Finding their way: themes in germ cell migration

https://doi.org/10.1016/j.ceb.2016.07.007Get rights and content

Embryonic germ cell migration is a vital component of the germline lifecycle. The translocation of germ cells from the place of origin to the developing somatic gonad involves several processes including passive movements with underlying tissues, transepithelial migration, cell adhesion dynamics, the establishment of environmental guidance cues and the ability to sustain directed migration. How germ cells accomplish these feats in established model organisms will be discussed in this review, with a focus on recent discoveries and themes conserved across species.

Introduction

Embryonic development involves the complex and coordinated movement of many cell types. In many metazoans, germ cells are specified at one location in the embryo and must translocate across a large distance to find the developing somatic gonad. This translocation often involves more than one process, including moving passively with underlying somatic cells, traversing epithelial barriers and responding to environmental guidance cues during active migration. As defects in any one of these processes can compromise fertility, the migration of germ cells is a critical component of the germline lifecycle and propagation of many metazoan species. As such, germ cell migration has been the subject of intense scientific interest for more than one hundred years [1, 2, 3] and has yielded a wealth of insights into the mechanisms of cell migration in the context of dynamically developing embryos. This review will focus on recent discoveries and highlight features and strategies shared by many model organisms.

Section snippets

Migratory paths of germ cells

Germ cell migration is investigated in an ever-growing number of organisms [4, 5••, 6, 7]. Established model organisms include mice, chicken, frogs, fruitflies and two teleost fish: zebrafish and medaka [8, 9•, 10, 11, 12, 13]. Despite divergence, features of overall path of embryonic germ cells can be remarkably similar between these species. For instance, germ cells are often specified at the posterior edge of the embryo or at the border between embryonic and extraembryonic tissues (Figure 1

Transepithelial migration

Germ cells in many species must cross an epithelium to reach the gonad. Insights into how germ cells traverse this barrier have been made through studies in mice and Drosophila. Several signal transduction pathways have been implicated in mouse germ cell exit from the hindgut, including Fibroblast growth factor (FGF) [21], Wnt [22] and Transforming growth factor beta (TGF-β) [23, 24]. Which cells produce and respond to these signals has yet to be determined, though the TGF-β responsive gene

Adhesion dynamics

Changes in adhesion are often observed in germ cells during endodermal exit or the initiation of active migration. The cell–cell adhesion protein E-cadherin is dynamically regulated in germ cells in many organisms (Figure 2). In zebrafish, E-cadherin is downregulated in migratory germ cells by the depletion of regulator of G-protein signaling 14a (Rgs14a) [27, 28]. Similarly, recent studies of isolated Xenopus germ cells using single cell force spectroscopy have shown that isolated migratory

Guidance to the gonad

Germ cells ultimately undergo active migration toward the developing somatic gonad. The high fidelity in which germ cells reach the gonad was noted early, leading to the postulate that germ cell migration is guided by environmental gradients [2, 3]. Initial support for this chemotaxis postulate came from two experimental strategies. First, in vitro studies demonstrated that mouse genital ridge explants attract isolated germ cells across a large distance [42, 43, 44]. Second, genetic screens in

Sustaining motility

Germ cells require both environmental guidance cues and the ability to initiate and sustain motility in order to reach the gonad. In some species germ cells must sustain directed migration for twenty-four to forty-eight hours (Figure 1). The study of zebrafish germ cell migration has proven fruitful for the discovery of autonomous motility factors (for a recent detailed review see [11]). One motility factor, Dead end regulates cell shape, actomyosin contractility, and cell–cell adhesion to

Post-migration fates

Germ cells that successfully reach the target tissue undergo several maturation steps to yield a functional gonad. The fate of germ cells that do not reach the gonad vary depending upon species. In Drosophila, Xenopus, and mice, germ cells that do not make it to the gonad eventually disappear, either through apoptosis or loss of germ cell fate [52, 53, 98, 99], while in zebrafish, mis-migrated germ cells persist quite some time during development [50]. Such differences may reflect a combined

Conclusions

The study of germ cell migration has yielded valuable insights into how cells navigate several tissues in a dynamic environment to reach their target. Despite mechanistic differences in migrational paths and guidance cues, the themes required for germ cell migration remain remarkably conserved across model organism species. In all species, the migration of germ cells is a multi-step process involving passive and active movements. While each translocation steps might seem distinct, emerging

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We would like to thank Alexey Soshnev for assistance with figures and members of the Lehmann lab for helpful discussions. This work was supported by the National Institutes of Health R37 HD49100 to RL. RL is a Howard Hughes Medical Institute Investigator. LJB is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-2235-15).

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