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Germline Stem Cells and Their Regulation in the Nematode Caenorhabditis elegans

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Transcriptional and Translational Regulation of Stem Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 786))

Abstract

C. elegans germline stem cells exist within a stem cell pool that is maintained by a single-celled mesenchymal niche and Notch signaling. Downstream of Notch signaling, a regulatory network governs stem cells and differentiation. Central to that network is the FBF RNA-binding protein, a member of the widely conserved PUF family that functions by either of two broadly conserved mechanisms to repress its target mRNAs. Without FBF, germline stem cells do not proliferate and they do not maintain their naïve, undifferentiated state. Therefore, FBF is a pivotal regulator of germline self-renewal. Validated FBF targets include several key differentiation regulators as well as a major cell cycle regulator. A genomic analysis identifies many other developmental and cell cycle regulators as likely FBF targets and suggests that FBF is a broad-spectrum regulator of the genome with >1,000 targets. A comparison of the FBF target list with similar lists for human PUF proteins, PUM1 and PUM2, reveals ∼200 shared targets. The FBF hub works within a network controlling self-renewal vs. differentiation. This network consists of classical developmental cell fate regulators and classical cell cycle regulators. Recent results have begun to integrate developmental and cell cycle regulation within the network. The molecular dynamics of the network remain a challenge for the future, but models are proposed. We suggest that molecular controls of C. elegans germline stem cells provide an important model for controls of stem cells more broadly.

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Acknowledgments

K.F. is supported by PF-10-127-01-DDC from the American Cancer Society. D.F.P. is supported by NIH Training Grant 5T32GM08349. J.K. is supported by NIH Grant R01GM069454. J.K. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706, USA

    Aaron Kershner, Kyle Friend & Douglas F. Porter

  2. Howard Hughes Medical Institute, Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI, USA

    Sarah L. Crittenden & Erika B. Sorensen

  3. Howard Hughes Medical Institute, Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706, USA

    Judith Kimble

  4. Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, USA

    Judith Kimble

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  1. Aaron Kershner
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  2. Sarah L. Crittenden
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  3. Kyle Friend
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  4. Erika B. Sorensen
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  5. Douglas F. Porter
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  6. Judith Kimble
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Correspondence to Judith Kimble .

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  1. , Anatomy and Neuroscience, University of Melbourne, VIC Grattan Street, Parkville, 3010, Victoria, Australia

    Gary Hime

  2. , Anatomy and Developmental Biology, Monash University, Monash University, Clayton, 3800, Victoria, Australia

    Helen Abud

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Kershner, A., Crittenden, S.L., Friend, K., Sorensen, E.B., Porter, D.F., Kimble, J. (2013). Germline Stem Cells and Their Regulation in the Nematode Caenorhabditis elegans . In: Hime, G., Abud, H. (eds) Transcriptional and Translational Regulation of Stem Cells. Advances in Experimental Medicine and Biology, vol 786. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6621-1_3

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