TY - JOUR
T1 - The miRNA Pathway Intrinsically Controls Self-Renewal of Drosophila Germline Stem Cells
AU - Park, Joseph K.
AU - Liu, Xiang
AU - Strauss, Tamara J.
AU - McKearin, Dennis M.
AU - Liu, Qinghua
N1 - Funding Information:
We thank Rosanna Addison and Jonathan Wu for excellent technical assistance and members of the Liu and McKearin labs as well as University of Texas Southwestern model organism labs for helpful discussions. Drs. Yi Liu, Jin Jiang, Helmut Kramer, Jean Maines, and Zain Paroo provided valuable discussion and critical comments on the manuscript. We also thank anonymous reviewers for important critiques that improved the manuscript. J.K.P. thanks the University of Texas Southwestern Medical Scientist Training Program for advice and support; Q.L. is a W.A. “Tex” Moncrief Jr. Scholar in Medical Research and a Damon Runyon Scholar, supported by the Damon Runyon Cancer Research Foundation (DRS-43). The work is also supported by a Welch grant (I-1608) and National Institutes of Health grants awarded to Q.L. (GM078163) and to D.M.M. (GM045820).
PY - 2007/3/20
Y1 - 2007/3/20
N2 - Stem cells uniquely self-renew and maintain tissue homoeostasis by differentiating into different cell types to replace aged or damaged cells [1]. During oogenesis of Drosophila melanogaster, self-renewal of germline stem cells (GSCs) requires both intrinsic signaling mechanisms and extrinsic signals from neighboring niche cells [2]. Emerging evidence suggests that microRNA (miRNA)-mediated translational regulation may also control Drosophila GSC self-renewal [3, 4]. It is unclear, however, whether the miRNA pathway functions within stem cells or niche cells to maintain GSCs. In Drosophila, Dicer-1 (Dcr-1) and the double-stranded RNA binding protein Loquacious (Loqs) catalyze miRNA biogenesis [3-5]. Here, we generate loqs knockout (loqsKO) flies by ends-out homologous recombination and show that loqs is essential for embryonic viability and ovarian GSC maintenance. Both developmental and miRNA processing defects are rescued by transgenic expression of Loqs-PB, but not Loqs-PA. Furthermore, mosaic germline analysis indicates that Loqs is required intrinsically for GSC maintenance. Consistently, GSCs are restored in loqs mutant ovaries by germline expression, but not somatic expression, of Loqs-PB. Together, these results demonstrate that Loqs-PB, but not Loqs-PA, is necessary and sufficient for Drosophila development and the miRNA pathway. Our study strongly suggests that miRNAs play an intrinsic, but not extrinsic, role in Drosophila female GSC self-renewal.
AB - Stem cells uniquely self-renew and maintain tissue homoeostasis by differentiating into different cell types to replace aged or damaged cells [1]. During oogenesis of Drosophila melanogaster, self-renewal of germline stem cells (GSCs) requires both intrinsic signaling mechanisms and extrinsic signals from neighboring niche cells [2]. Emerging evidence suggests that microRNA (miRNA)-mediated translational regulation may also control Drosophila GSC self-renewal [3, 4]. It is unclear, however, whether the miRNA pathway functions within stem cells or niche cells to maintain GSCs. In Drosophila, Dicer-1 (Dcr-1) and the double-stranded RNA binding protein Loquacious (Loqs) catalyze miRNA biogenesis [3-5]. Here, we generate loqs knockout (loqsKO) flies by ends-out homologous recombination and show that loqs is essential for embryonic viability and ovarian GSC maintenance. Both developmental and miRNA processing defects are rescued by transgenic expression of Loqs-PB, but not Loqs-PA. Furthermore, mosaic germline analysis indicates that Loqs is required intrinsically for GSC maintenance. Consistently, GSCs are restored in loqs mutant ovaries by germline expression, but not somatic expression, of Loqs-PB. Together, these results demonstrate that Loqs-PB, but not Loqs-PA, is necessary and sufficient for Drosophila development and the miRNA pathway. Our study strongly suggests that miRNAs play an intrinsic, but not extrinsic, role in Drosophila female GSC self-renewal.
KW - DEVBIO
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U2 - 10.1016/j.cub.2007.01.060
DO - 10.1016/j.cub.2007.01.060
M3 - Article
C2 - 17320391
AN - SCOPUS:33947107476
SN - 0960-9822
VL - 17
SP - 533
EP - 538
JO - Current Biology
JF - Current Biology
IS - 6
ER -