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A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans

Nature volume 417, pages 660–663 (2002)Cite this article

Abstract

Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes1. The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell2,3. FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF (‘fem-3 mRNA binding factor’), were originally discovered as regulators of germline sex determination4. Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle5,6. FBF belongs to the PUF family (‘Pumilio and FBF’) of RNA-binding proteins7. Pumilio controls germline stem cells in Drosophila females8,9, and, in lower eukaryotes, PUF proteins promote continued mitoses10,11. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.

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Figure 1: FBF is required for germline stem cells.
Figure 2: FBF-1 controls GLD-1 expression.
Figure 3: FBF binds specifically to the gld-1 3′UTR.
Figure 4: PUF protein regulation of cell fates.

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Acknowledgements

We thank R. Reijo Pera for sharing unpublished observations; and members of the Kimble and Wickens laboratories, T. Schedl and E. Goodwin for comments on the manuscript. J.K. is an investigator of the Howard Hughes Medical Institute. M.W. is supported by the National Institutes of Health.

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Author notes

  1. Maria Gallegos

    Present address: Department of Anatomy, The University of California, San Francisco, California, 94143, USA

  2. Andrei G. Petcherski

    Present address: Wormbase, Caltech 156-29, Pasadena, California, 91125, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, University of Wisconsin–Madison, Madison, Wisconsin, 53706, USA

    Sarah L. Crittenden & Judith Kimble

  2. Department of Biochemistry, University of Wisconsin–Madison, Madison, Wisconsin, 53706, USA

    David S. Bernstein, Andrei G. Petcherski, Marvin Wickens & Judith Kimble

  3. Program in Cellular and Molecular Biology, University of Wisconsin–Madison, Madison, Wisconsin, 53706, USA

    Jennifer L. Bachorik, Beth E. Thompson & Maria Gallegos

  4. Program in Molecular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, 73104, USA

    Gary Moulder & Robert Barstead

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Correspondence to Judith Kimble.

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Crittenden, S., Bernstein, D., Bachorik, J. et al. A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417, 660–663 (2002). https://doi.org/10.1038/nature754

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