QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 31 March 2009
doi: 10.1242/dev.025999

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.025999v1 136/9/1497    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, J.-Y. Articles by Ruohola-Baker, H. Search for Related Content PubMed PubMed Citation Articles by Yu, J.-Y. Articles by Ruohola-Baker, H. Social Bookmarking                         What's this?

Dicer-1-dependent Dacapo suppression acts downstream of Insulin receptor in regulating cell division of Drosophila germline stem cells

Jenn-Yah Yu^1,*,, Steven H. Reynolds^1,*, Steve D. Hatfield^1,, Halyna R. Shcherbata^1,, Karin A. Fischer¹, Ellen J. Ward¹, Dang Long², Ye Ding² and Hannele Ruohola-Baker^1,¶

¹ Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
² Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, USA.

^¶ Author for correspondence (e-mail: hannele{at}u.washington.edu)

Accepted 2 March 2009

It is important to understand the regulation of stem cell division because defects in this process can cause altered tissue homeostasis or cancer. The cyclin-dependent kinase inhibitor Dacapo (Dap), a p21/p27 homolog, acts downstream of the microRNA (miRNA) pathway to regulate the cell cycle in Drosophila melanogaster germline stem cells (GSCs). Tissue-extrinsic signals, including insulin, also regulate cell division of GSCs. We report that intrinsic and extrinsic regulators intersect in GSC division control; the Insulin receptor (InR) pathway regulates Dap levels through miRNAs, thereby controlling GSC division. Using GFP-dap 3'UTR sensors in vivo, we show that in GSCs the dap 3'UTR is responsive to Dicer-1, an RNA endonuclease III required for miRNA processing. Furthermore, the dap 3'UTR can be directly targeted by miR-7, miR-278 and miR-309 in luciferase assays. Consistent with this, miR-278 and miR-7 mutant GSCs are partially defective in GSC division and show abnormal cell cycle marker expression, respectively. These data suggest that the GSC cell cycle is regulated via the dap 3'UTR by multiple miRNAs. Furthermore, the GFP-dap 3'UTR sensors respond to InR but not to TGF-β signaling, suggesting that InR signaling utilizes Dap for GSC cell cycle regulation. We further demonstrate that the miRNA-based Dap regulation may act downstream of InR signaling; Dcr-1 and Dap are required for nutrition-dependent cell cycle regulation in GSCs and reduction of dap partially rescues the cell cycle defect of InR-deficient GSCs. These data suggest that miRNA- and Dap-based cell cycle regulation in GSCs can be controlled by InR signaling.

Key words: Cell cycle, Dacapo, Stem cells, Drosophila

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

Insulin signals for control of germline stem cell divisions

Development 2009 136: e902. [Full Text]  

This article has been cited by other articles:

				J.-Y. Yu, S. H. Reynolds, S. D. Hatfield, H. R. Shcherbata, K. A. Fischer, E. J. Ward, D. Long, Y. Ding, and H. Ruohola-Baker Dicer-1-dependent Dacapo suppression acts downstream of insulin receptor in regulating cell division of Drosophila germline stem cells J. Cell Sci., May 1, 2009; 122(9): e1 - e1. [Full Text]