Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling

Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA.
Development (Impact Factor: 6.46). 03/2012; 139(9):1547-56. DOI: 10.1242/dev.077412
Source: PubMed


In the Drosophila ovary, bone morphogenetic protein (BMP) ligands maintain germline stem cells (GSCs) in an undifferentiated state. The activation of the BMP pathway within GSCs results in the transcriptional repression of the differentiation factor bag of marbles (bam). The Nanos-Pumilio translational repressor complex and the miRNA pathway also help to promote GSC self-renewal. How the activities of different transcriptional and translational regulators are coordinated to keep the GSC in an undifferentiated state remains uncertain. Data presented here show that Mei-P26 cell-autonomously regulates GSC maintenance in addition to its previously described role of promoting germline cyst development. Within undifferentiated germ cells, Mei-P26 associates with miRNA pathway components and represses the translation of a shared target mRNA, suggesting that Mei-P26 can enhance miRNA-mediated silencing in specific contexts. In addition, disruption of mei-P26 compromises BMP signaling, resulting in the inappropriate expression of bam in germ cells immediately adjacent to the cap cell niche. Loss of mei-P26 results in premature translation of the BMP antagonist Brat in germline stem cells. These data suggest that Mei-P26 has distinct functions in the ovary and participates in regulating the fates of both GSCs and their differentiating daughters.

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    • "The underlying mechanism has been suggested to involve miRNAs, as both Mei-P26 and Brat are able to bind Argonaute- 1 (Ago1), which is a known component of the miRNA pathway [32]. Interestingly, Mei-P26 activates miRNA-dependent silencing of certain mRNAs, including brat, in GSCs [25] [33], but inhibits the miRNA pathway in differentiating germline cysts [32]. In fact, these context-dependent opposing roles translate into distinct biological roles as Mei-P26 is required for stem cell maintenance in GSCs and differentiation in GCs. "
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    • "In contrast, overexpressing a form of Mei-P26 lacking the NHL domain, which mediates specific protein–protein interactions, did not affect dMyc levels (Figure S2B). Equivalent amounts of fulllength Mei-P26 and the truncated version were found to be expressed with the GAL4/UAS system in the Drosophila ovary (Li et al. 2012). Thus, both the ubiquitin ligase activity (Herranz et al. 2010) and the NHL domain (this work) of Mei-P26 are required to target dMyc for degradation . "
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    • "In wild type germaria, the two GSC are characterized by round Spectrin accumulation, while as cells differentiate towards the posterior, Spectrin is involved in the formation of the fusome and it acquires a branched morphology. The fusome is a germline specific structure with branching arms that extend through each intercellular bridge in the cyst [36]. A normal GSC differentiation process was visible in the heterozygous lin-28dF30/+ germaria (Figure 6A and 6A’). "
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