Abstract
The Argonaute-family proteins play crucial roles in small-RNA-mediated gene regulation. In Drosophila, previous studies have demonstrated that Piwi, one member of the PIWI subfamily of Argonaute proteins, plays an essential role in regulating the fate of germline stem cells (GSCs). However, whether other Argonaute proteins also play similar roles remains elusive. Here, we show that overexpression of Argonaute 1 (AGO1) protein, another subfamily (AGO) of the Argonaute proteins, leads to GSC overproliferation, whereas loss of Ago1 results in the loss of GSCs. Combined with germline clonal analyses of Ago1, these findings strongly support the argument that Ago1 plays an essential and intrinsic role in the maintenance of GSCs. In contrast to previous observations of Piwi function in the maintenance of GSCs, we show that AGO1 is not required for bag of marbles (bam) silencing and probably acts downstream or parallel of bam in the regulation of GSC fate. Given that AGO1 serves as a key component of the miRNA pathway, we propose that an AGO1-dependent miRNA pathway probably plays an instructive role in repressing GSC/cystoblast differentiation.
Highlights
In Drosophila ovary, germline stem cells (GSC) provide an attractive system for investigating the regulatory mechanisms that determine stem cell fate (Lin, 2002; Spradling et al, 2001)
Ectopic Argonaute 1 (AGO1) expression increases the number of GSC-like cells To explore the potential role of Ago1 in the regulation of GSC fate, we overexpressed Ago1 in germaria by expressing an Ago1 cDNA under the control of the heat-shock promoter P{hs-Ago1} and applying daily heat-shock treatment (Kataoka et al, 2001)
We showed that overexpression of AGO1 leads to GSC overproliferation, whereas loss of Ago1 results in the loss of GSCs
Summary
In Drosophila ovary, germline stem cells (GSC) provide an attractive system for investigating the regulatory mechanisms that determine stem cell fate (Lin, 2002; Spradling et al, 2001). Studies from several laboratories have identified the genes that are essential for GSC fate determination Both the bag of marbles (bam) and benign gonial cell neoplasm (bgcn) genes are known to act autonomously in the germline and are required for cystoblast (CB) differentiation (Lavoie et al, 1999; McKearin and Ohlstein, 1995). Recent data showed that Pelota, another putative translational repressor, plays a similar role in controlling GSC fate in a bam-independent manner (Xi et al, 2005). These findings suggest that cellautonomous translational control could contribute a great deal to GSC regulation
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