A Regulatory Network of Drosophila Germline Stem Cell Self-Renewal

Dong, Yan; Neumüller, Ralph A.; Buckner, Michael; Ayers, Kathleen; Li, Hua; Hu, Yanhui; Yang‐Zhou, Donghui; Pan, Lei; Wang, Xiaoxi; Kelley, Colleen; Vinayagam, Arunachalam; Binari, Richard; Randklev, Sakara; Perkins, Lizabeth A.; Xie, Ting; Cooley, Lynn; Perrimon, Norbert

doi:10.1016/j.devcel.2014.01.020

Cited by 133 publications

(203 citation statements)

References 62 publications

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“…nito was identified from our previous RNAi screen in Drosophila GSCs (19). Specifically, RNAi knockdown of nito driven by the germ-line-specific MTD-Gal4 driver resulted in complete sterility in females.…”

Section: Resultsmentioning

confidence: 99%

spenito is required for sex determination in Drosophila melanogaster

Dong

Perrimon

2015

Proc. Natl. Acad. Sci. U.S.A.

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Sex-lethal (Sxl) encodes the master regulator of the sex determination pathway in Drosophila and acts by controlling sex identity in both soma and germ line. In females Sxl maintains its own expression by controlling the alternative splicing of its own mRNA. Here, we identify a novel sex determination gene, spenito (nito) that encodes a SPEN family protein. Loss of nito activity results in stem cell tumors in the female germ line as well as female-to-male somatic transformations. We show that Nito is a ubiquitous nuclear protein that controls the alternative splicing of the Sxl mRNA by interacting with Sxl protein and pre-mRNA, suggesting that it is directly involved in Sxl auto-regulation. Given that SPEN family proteins are frequently mutated in cancers, our results suggest that these factors might be implicated in tumorigenesis through splicing regulation.germ-line stem cell | sex determination | alternative splicing S ex determination in Drosophila is under the control of the master regulatory gene Sex-lethal (Sxl) (1). Sxl acts downstream of the X-chromosome counting mechanism and encodes a female-specific RNA binding protein. Once activated, Sxl maintains its own expression by regulating the alternative splicing of its pre-mRNA. Sxl controls female fate by controlling somatic and germ-line sex identity as well as dosage compensation (2). In female somatic cells, Sxl controls the alternative splicing of transformer (tra), which together with transformer2 (tra2) controls the alternative splicing of doublesex (dsx) and fruitless (fru). dsx and fru in turn encode sex-specific transcription factors that control male versus female morphology, physiology, and behavior (3, 4). In addition, Sxl represses the male-specific dosage compensation system by regulating male-specific lethal 2 (msl-2) both at the level of alternative splicing and translational control (5

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Section: Resultsmentioning

confidence: 99%

spenito is required for sex determination in Drosophila melanogaster

Dong

Perrimon

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Some evidence suggests that such regulation exists. For example, knockdown of SET1 causes an oogenesis defect, but does not affect neuronal development (54). It will be interesting to see whether O-GlcNAc plays a role in gender-specific or tissue-specific gene expression.…”

Section: O-glcnac Cycling Occurs At Sites Associated With Polycomb Anmentioning

confidence: 99%

Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation

Akan

Love

Harwood

et al. 2016

Journal of Biological Chemistry

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“…In particular, results from various large-scale screens have been included. Among these are germline and maternal effect screens using the MTD-Gal4 driver (Staller et al 2013;Sopko et al 2014;Yan et al 2014), a muscle screen using the muscle Dmef2-Gal4 line (Perrimon and Randkelv, unpublished results), a screen in gut stem cells using the esg-Gal4 (Zeng et al 2015), and a screen of maternally expressed genes involved in embryonic patterning (Liu and Lasko 2015). As of May 2015, and specific for the TRiP stocks, the RSVP contains 8334 data entries for 5202 TRiP stocks representing 3735 fly genes.…”

Section: Validation Of the Trip Linesmentioning

confidence: 99%

The Transgenic RNAi Project at Harvard Medical School: Resources and Validation

et al. 2015

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To facilitate large-scale functional studies in Drosophila, the Drosophila Transgenic RNAi Project (TRiP) at Harvard Medical School (HMS) was established along with several goals: developing efficient vectors for RNAi that work in all tissues, generating a genome-scale collection of RNAi stocks with input from the community, distributing the lines as they are generated through existing stock centers, validating as many lines as possible using RT-qPCR and phenotypic analyses, and developing tools and web resources for identifying RNAi lines and retrieving existing information on their quality. With these goals in mind, here we describe in detail the various tools we developed and the status of the collection, which is currently composed of 11,491 lines and covering 71% of Drosophila genes. Data on the characterization of the lines either by RT-qPCR or phenotype is available on a dedicated website, the RNAi Stock Validation and Phenotypes Project (RSVP, http://www.flyrnai.org/RSVP.html), and stocks are available from three stock centers, the Bloomington Drosophila Stock Center (United States), National Institute of Genetics (Japan), and TsingHua Fly Center (China). KEYWORDS RNAi; Drosophila; screens; phenotypes; functional genomics A striking finding from the genomic revolution and wholegenome sequencing is the amount of information missing on gene function. Although Drosophila is arguably the bestunderstood multicellular organism and a proven model system for human diseases, mutations mapped to specific genes with readily detectable phenotypes have been isolated for 15% of the .13919 annotated fly coding genes (http:// flybase.org/; FlyBase R6.06). The lack of information on the majority of genes (the "phenotype gap") suggests that researchers have been unable to either assay their roles experimentally and/or resolve issues of functional redundancy. In addition, some phenotypes may be only detected on specific diets and environments. Further, our understanding of the function of many genes for which we have some information is limited by pleiotropy, whereby an earlier function of the gene prevents analysis of later functions.The availability of in vivo RNAi has revolutionized the ability of Drosophila researchers to disrupt the activity of single genes with spatial and temporal resolution (Dietzl et al. 2007; see review by Perrimon et al. 2010), and thus address the phenotype gap. Motivated by the power of the approach and the needs of the community, three large-scale efforts, the Vienna Drosophila RNAi Center (VDRC, http:// stockcenter.vdrc.at/control/main), the National Institute of Genetics (NIG, http://www.shigen.nig.ac.jp/fly/nigfly/index.jsp), and the Drosophila Transgenic RNAi Project (TRiP) at Harvard Medical School (HMS) (http://www.flyrnai.org/TRiP-HOME. html) have over the years generated large numbers of RNAi lines that aim to cover all Drosophila genes. These resources are proving invaluable to address a myriad of questions in various biological and biomedical fields including but not limite...

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A Regulatory Network of Drosophila Germline Stem Cell Self-Renewal

Cited by 133 publications

References 62 publications

spenito is required for sex determination in Drosophila melanogaster

spenito is required for sex determination in Drosophila melanogaster

Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation

The Transgenic RNAi Project at Harvard Medical School: Resources and Validation

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