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Science 12 September 2003:
Vol. 301. no. 5639, pp. 1547 - 1550
DOI: 10.1126/science.1087795
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Reports

Orientation of Asymmetric Stem Cell Division by the APC Tumor Suppressor and Centrosome

Yukiko M. Yamashita,1 D. Leanne Jones,1 Margaret T. Fuller1,2*

Stem cell self-renewal can be specified by local signals from the surrounding microenvironment, or niche. However, the relation between the niche and the mechanisms that ensure the correct balance between stem cell self-renewal and differentiation is poorly understood. Here, we show that dividing Drosophila male germline stem cells use intracellular mechanisms involving centrosome function and cortically localized Adenomatous Polyposis Coli tumor suppressor protein to orient mitotic spindles perpendicular to the niche, ensuring a reliably asymmetric outcome in which one daughter cell remains in the niche and self-renews stem cell identity, whereas the other, displaced away, initiates differentiation.

1 Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305–5329, USA.
2 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305–5329, USA.

* To whom correspondence should be addressed. E-mail: fuller{at}cmgm.stanford.edu

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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J.-C. Labbe, E. K. McCarthy, and B. Goldstein (2004)
J. Cell Biol. 167, 245-256
   Abstract »    Full Text »    PDF »
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L. Gilboa and R. Lehmann (2004)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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H. J. Lawrence (2004)
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   Full Text »    PDF »
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H. Maekawa and E. Schiebel (2004)
Genes & Dev. 18, 1709-1724
   Abstract »    Full Text »    PDF »
STEM CELL IN GASTROINTESTINAL STRUCTURE AND NEOPLASTIC DEVELOPMENT.
M Brittan and N A Wright (2004)
Gut 53, 899-910
   Full Text »    PDF »
A Misexpression Screen Reveals Effects of bag-of-marbles and TGF{beta} Class Signaling on the Drosophila Male Germ-Line Stem Cell Lineage.
C. Schulz, A. A. Kiger, S. I. Tazuke, Y. M. Yamashita, L. C. Pantalena-Filho, D. L. Jones, C. G. Wood, and M. T. Fuller (2004)
Genetics 167, 707-723
   Abstract »    Full Text »    PDF »
Regeneration of Male Germline Stem Cells by Spermatogonial Dedifferentiation in Vivo.
C. Brawley and E. Matunis (2004)
Science 304, 1331-1334
   Abstract »    Full Text »    PDF »
Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm.
G. Prindull and D. Zipori (2004)
Blood 103, 2892-2899
   Abstract »    Full Text »    PDF »
Abstracts.
(2004)
Gut 53, a1-a123
   Full Text »    PDF »
Convergence of Wnt, {beta}-Catenin, and Cadherin Pathways.
W. J. Nelson and R. Nusse (2004)
Science 303, 1483-1487
   Abstract »    Full Text »    PDF »
Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells.
Y. Li, B. Welm, K. Podsypanina, S. Huang, M. Chamorro, X. Zhang, T. Rowlands, M. Egeblad, P. Cowin, Z. Werb, et al. (2003)
PNAS 100, 15853-15858
   Abstract »    Full Text »    PDF »
Centrosomes lead stem cell orientation.
N. LeBrasseur (2003)
J. Cell Biol. 162, 1181
   Full Text »    PDF »


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