Abstract
Stem cells generate self-renewing and differentiating progeny over many rounds of asymmetric divisions. How stem cell growth rate and size are maintained over time remains unknown. We isolated mutations in a Drosophila melanogaster gene, wicked (wcd), which induce premature differentiation of germline stem cells (GSCs). Wcd is a member of the U3 snoRNP complex required for pre-ribosomal RNA maturation. This general function of Wcd contrasts with its specific requirement for GSC self-renewal. However, live imaging of GSCs within their niche revealed a pool of Wcd-forming particles that segregate asymmetrically into the GSCs on mitosis, independently of the Dpp signal sent by the niche. A fraction of Wcd also segregated asymmetrically in dividing larval neural stem cells (NSCs). In the absence of Wcd, NSCs became smaller and produced fewer neurons. Our results show that regulation of ribosome synthesis is a crucial parameter for stem cell maintenance and function.
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Acknowledgements
We are especially grateful to Danièle Hernandez-Verdun, Bruno Bello, Frank Hirth, Andrew Vaughan and the Imaging facilities at IJM for experimental advice; to Danièle Hernandez-Verdun, Acaimo Gonzalez-Reyes, Antoine Guichet, Juliette Mathieu, Emily Richardson and Ralph Neumuller for critical reading. We are also grateful for reagents provided by Danièle Hernandez-Verdun, Joe Gall, Acaimo Gonzalez-Reyes, Fumio Matsuzaki, Christophe Antoniewski, Antoine Guichet, Christian Lehner, Alex Gould, Tzumin Lee, Barry Thompson, DHSB (Iowa University) and Bloomington Drosophila Stock center. We wish to thank Franck Pichaud (MRC-LMCB, UCL) in whose lab part of this work was performed. This work was funded by grants to J.R.H. (CNRS, ARC # 3802, and ANR # 06-JCJC-0092-01), P.F. (ARC post-doctoral fellowhip and EMBO long term fellowship), CM (CNRS), J.A.L. (CNRS, ARC# 3802) Ch.M. and Y.B. (CNRS, Curie).
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Fichelson, P., Moch, C., Ivanovitch, K. et al. Live-imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila. Nat Cell Biol 11, 685–693 (2009). https://doi.org/10.1038/ncb1874
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DOI: https://doi.org/10.1038/ncb1874
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