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Reply to: "On the robustness of germ cell migration and microRNA-mediated regulation of chemokine signaling"

Nature Genetics volume 45, pages 1266–1267 (2013)Cite this article

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Staton et al. reply:

Germ cells need to migrate from their site of origin to the future gonad in zebrafish. To do so, they use the Sdf1a chemokine signaling pathway1. Dynamic expression of the ligand Sdf1a is important for germ cell migration, as germ cells closely follow the changing expression gradient of Sdf1a2,3. Sdf1a constitutes a short-range attracting signal that is sensed by germ cells through the receptor Cxcr4 (refs. 3,4). Sdf1a ligand is also bound by Cxcr7, a proposed decoy receptor that is thought to titrate excess Sdf1a protein, acting as a protein sink5. Our previous study showed that microRNAs (miRNAs) provide robustness to this process in zebrafish, and we demonstrated that miR-430 regulates the 3′ UTRs of sdf1a and cxcr7b, with loss of this regulation reducing the fidelity of germ cell migration to the future gonad6. This miRNA activity provides an additional layer of regulation by which the embryo shapes the dynamic expression of sdf1a mRNA during germ cell migration. Goudarzi and colleagues raise several questions about the results of our paper demonstrating the role of miR-430 in promoting robustness during primordial germ cell (PGC) migration6. Their challenge hinges on their inability to observe increased mislocalization of PGCs in MZdicer embryos when monitoring germ cells through the expression of the vasa gene. However, when monitoring germ cells using nanos expression, Goudarzi et al. show an increase in the frequency of germ cell mislocalization in dicer-mutant compared to wild-type embryos, albeit the effect of miRNA loss is weaker than in our study.

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Figure 1: Loss of miRNAs results in an increase in the frequency of embryos with mislocalized germ cells.
Figure 2: miR-430–mediated regulation of sdf1a and cxcr7b guards against the mismigration effects of variation in gene dosage.

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Acknowledgements

The authors would like to thank A. Bonneau, K. DiVito and E. Fleming for assistance with reagents and zebrafish care.

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Authors and Affiliations

  1. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA

    Alison A Staton & Antonio J Giraldez

  2. Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA

    Holger Knaut

  3. Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut, USA

    Antonio J Giraldez

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  1. Alison A Staton
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Correspondence to Antonio J Giraldez.

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Staton, A., Knaut, H. & Giraldez, A. Reply to: "On the robustness of germ cell migration and microRNA-mediated regulation of chemokine signaling". Nat Genet 45, 1266–1267 (2013). https://doi.org/10.1038/ng.2812

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