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Integrin-dependent anchoring of a stem-cell niche

Abstract

Interactions between stem cells and their surrounding microenvironment, or niche, are critical for the establishment and maintenance of stem-cell properties1. The adult Drosophila testis contains a morphologically discrete stem-cell niche, the 'hub'2,3,4. The small cluster of non-dividing, somatic hub cells at the anterior tip of the fly testis is contacted by the germline stem cells (GSCs)5, which retain their stem-cell character through the direct association with the hub6. Here we show that integrin-mediated adhesion is important for maintaining the correct position of embryonic hub cells during gonad morphogenesis. The misplaced hub in integrin-deficient embryos directs the orientation of cell divisions in the presumptive GSCs, a hallmark of the active germline stem-cell niche. A decrease in integrin-mediated adhesion in adult testes, which resulted in a loss of the hub and the stem-cell population, revealed the importance of hub-cell anchoring. Finally, we show that an extracellular matrix (ECM) is present around the gonad during late embryogenesis and that this ECM is defective in integrin-deficient gonads. On the basis of our data, we propose that integrins are required for the attachment of the hub cells to the ECM, which is essential for maintaining the stem-cell niche.

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Figure 1: The hub cells are mispositioned in integrin-mutant embryos.
Figure 2: Integrin and talin expression in somatic cells in the gonad.
Figure 3: Integrins assemble an ECM around the embryonic gonad.
Figure 4: Spindle orientation in wild-type and integrin-mutant embryonic gonads.
Figure 5: Phenotypes of talin RNAi in adult testes.

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Acknowledgements

We thank S. Baumgartner, L. Cooley, R. Lehmann, J. Raff, R. Basto and the Developmental Studies Hybridoma Bank (University of Iowa, IA) for antibodies; B. Dickson and F. Schnorrer for RNAi fly stocks, the Drosophila Genomics Resource Center (Kyoto Institute of Technology) for the tj-GAL4 line; T. Clandinin (Stanford University, Palo Alto, CA) and U. Tepass for cadherin fly stocks; and S. Choksi, L. Jones (UCSD, San Diego, CA) and U. Tepass for critical reading of the manuscript. This work was supported by a Natural Sciences and Engineering Research Council of Canada grant to D.G., Wellcome Trust grants to N.H.B. (69943) and D.D. (72817), a Human Frontiers Science Program Long Term Fellowship and a Development Travelling Fellowship to G.T.

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Correspondence to Guy Tanentzapf.

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Supplementary figures S1, S2, S3, S4 and S5 (PDF 1241 kb)

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Tanentzapf, G., Devenport, D., Godt, D. et al. Integrin-dependent anchoring of a stem-cell niche. Nat Cell Biol 9, 1413–1418 (2007). https://doi.org/10.1038/ncb1660

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