{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:32:43Z","timestamp":1784622763849,"version":"3.55.0"},"reference-count":59,"publisher":"The Company of Biologists","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/dev.077412","type":"journal-article","created":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T01:59:26Z","timestamp":1332467966000},"page":"1547-1556","source":"Crossref","is-referenced-by-count":67,"title":["Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling"],"prefix":"10.1242","volume":"139","author":[{"given":"Yun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Z.","family":"Maines","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6m\u00fcr Y.","family":"Tastan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M.","family":"McKearin","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buszczak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606411024000_R1","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1101\/gad.6.12a.2312","article-title":"Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos","volume":"6","author":"Barker","year":"1992","journal-title":"Genes Dev."},{"key":"2021042606411024000_R2","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.cell.2006.01.038","article-title":"Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells","volume":"124","author":"Betschinger","year":"2006","journal-title":"Cell"},{"key":"2021042606411024000_R3","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1242\/dev.01076","article-title":"Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling","volume":"131","author":"Casanueva","year":"2004","journal-title":"Development"},{"key":"2021042606411024000_R4","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1261\/rna.1364909","article-title":"Multiple independent domains of dGW182 function in miRNA-mediated repression in Drosophila","volume":"15","author":"Chekulaeva","year":"2009","journal-title":"RNA"},{"key":"2021042606411024000_R5","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1242\/dev.00325","article-title":"A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell","volume":"130","author":"Chen","year":"2003","journal-title":"Development"},{"key":"2021042606411024000_R6","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.cub.2003.09.033","article-title":"Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells","volume":"13","author":"Chen","year":"2003","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cub.2005.01.004","article-title":"Gene circuitry controlling a stem cell niche","volume":"15","author":"Chen","year":"2005","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R8","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1101\/gad.8.5.614","article-title":"orb is required for anteroposterior and dorsoventral patterning during Drosophila oogenesis","volume":"8","author":"Christerson","year":"1994","journal-title":"Genes Dev."},{"key":"2021042606411024000_R9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrg2916","article-title":"Small RNA sorting: matchmaking for Argonautes","volume":"12","author":"Czech","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2021042606411024000_R10","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1242\/dev.125.15.2781","article-title":"Morphogenesis of the Drosophila fusome and its implications for oocyte specification","volume":"125","author":"de Cuevas","year":"1998","journal-title":"Development"},{"key":"2021042606411024000_R11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nsmb.1405","article-title":"GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay","volume":"15","author":"Eulalio","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021042606411024000_R12","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1242\/dev.125.4.679","article-title":"Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells","volume":"125","author":"Forbes","year":"1998","journal-title":"Development"},{"key":"2021042606411024000_R13","doi-asserted-by":"crossref","first-page":"e236","DOI":"10.1371\/journal.pbio.0030236","article-title":"Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein","volume":"3","author":"Forstemann","year":"2005","journal-title":"PLoS Biol."},{"key":"2021042606411024000_R14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1126\/science.1140861","article-title":"Male and female Drosophila germline stem cells: two versions of immortality","volume":"316","author":"Fuller","year":"2007","journal-title":"Science"},{"key":"2021042606411024000_R15","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1073\/pnas.0509260103","article-title":"Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster","volume":"103","author":"Gerber","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606411024000_R16","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cub.2004.05.049","article-title":"Repression of primordial germ cell differentiation parallels germ line stem cell maintenance","volume":"14","author":"Gilboa","year":"2004","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R17","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature09267","article-title":"Mammalian microRNAs predominantly act to decrease target mRNA levels","volume":"466","author":"Guo","year":"2010","journal-title":"Nature"},{"key":"2021042606411024000_R18","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.cell.2009.01.053","article-title":"nhl-2 Modulates microRNA activity in Caenorhabditis elegans","volume":"136","author":"Hammell","year":"2009","journal-title":"Cell"},{"key":"2021042606411024000_R19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.devcel.2010.11.019","article-title":"Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling","volume":"20","author":"Harris","year":"2011","journal-title":"Dev. Cell"},{"key":"2021042606411024000_R20","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1242\/dev.125.8.1407","article-title":"The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4","volume":"125","author":"Hudson","year":"1998","journal-title":"Development"},{"key":"2021042606411024000_R21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.devcel.2009.06.008","article-title":"miR-184 has multiple roles in Drosophila female germline development","volume":"17","author":"Iovino","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042606411024000_R22","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/338646a0","article-title":"The Drosophila posterior-group gene nanos functions by repressing hunchback activity","volume":"338","author":"Irish","year":"1989","journal-title":"Nature"},{"key":"2021042606411024000_R23","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.cub.2007.01.050","article-title":"Dcr-1 maintains Drosophila ovarian stem cells","volume":"17","author":"Jin","year":"2007","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R24","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1073\/pnas.0830856100","article-title":"An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells","volume":"100","author":"Kai","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606411024000_R25","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ncb2105","article-title":"A Pumilio-induced RNA structure switch in p27-3\u2032 UTR controls miR-221 and miR-222 accessibility","volume":"12","author":"Kedde","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"2021042606411024000_R26","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1128\/MCB.19.4.2505","article-title":"Requirement of RBP9, a Drosophila Hu homolog, for regulation of cystocyte differentiation and oocyte determination during oogenesis","volume":"19","author":"Kim-Ha","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"2021042606411024000_R27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1242\/dev.115.1.75","article-title":"The Drosophila orb gene is predicted to encode sex-specific germline RNA-binding proteins and has localized transcripts in ovaries and early embryos","volume":"115","author":"Lantz","year":"1992","journal-title":"Development"},{"key":"2021042606411024000_R28","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1101\/gad.8.5.598","article-title":"The Drosophila orb RNA-binding protein is required for the formation of the egg chamber and establishment of polarity","volume":"8","author":"Lantz","year":"1994","journal-title":"Genes Dev."},{"key":"2021042606411024000_R29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1006\/dbio.1999.9346","article-title":"Localization and function of Bam protein require the benign gonial cell neoplasm gene product","volume":"212","author":"Lavoie","year":"1999","journal-title":"Dev. Biol."},{"key":"2021042606411024000_R30","doi-asserted-by":"crossref","first-page":"9304","DOI":"10.1073\/pnas.0901452106","article-title":"Bam and Bgcn antagonize Nanos-dependent germ-line stem cell maintenance","volume":"106","author":"Li","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606411024000_R31","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1101\/gad.1820709","article-title":"Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3\u2032 UTR","volume":"23","author":"Liu","year":"2009","journal-title":"Genes Dev."},{"key":"2021042606411024000_R32","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1261\/rna.723707","article-title":"Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes","volume":"13","author":"Liu","year":"2007","journal-title":"RNA"},{"key":"2021042606411024000_R33","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1242\/dev.121.9.2937","article-title":"A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells","volume":"121","author":"McKearin","year":"1995","journal-title":"Development"},{"key":"2021042606411024000_R34","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/0092-8674(95)90353-4","article-title":"Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos","volume":"80","author":"Murata","year":"1995","journal-title":"Cell"},{"key":"2021042606411024000_R35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nbt0102-87","article-title":"A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications","volume":"20","author":"Nagai","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"2021042606411024000_R36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature07014","article-title":"Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage","volume":"454","author":"Neumuller","year":"2008","journal-title":"Nature"},{"key":"2021042606411024000_R37","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1242\/dev.124.18.3651","article-title":"Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells","volume":"124","author":"Ohlstein","year":"1997","journal-title":"Development"},{"key":"2021042606411024000_R38","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/genetics\/155.4.1809","article-title":"The Drosophila cystoblast differentiation factor, benign gonial cell neoplasm, is related to DExH-box proteins and interacts genetically with bag-of-marbles","volume":"155","author":"Ohlstein","year":"2000","journal-title":"Genetics"},{"key":"2021042606411024000_R39","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/genetics\/155.4.1757","article-title":"Genetic studies of mei-P26 reveal a link between the processes that control germ cell proliferation in both sexes and those that control meiotic exchange in Drosophila","volume":"155","author":"Page","year":"2000","journal-title":"Genetics"},{"key":"2021042606411024000_R40","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cub.2007.01.060","article-title":"The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells","volume":"17","author":"Park","year":"2007","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R41","doi-asserted-by":"crossref","first-page":"e235","DOI":"10.1371\/journal.pbio.0030235","article-title":"Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells","volume":"3","author":"Saito","year":"2005","journal-title":"PLoS Biol."},{"key":"2021042606411024000_R42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0925-4773(01)00654-2","article-title":"Identification of a transcriptional regulatory region for germline-specific expression of vasa gene in Drosophila melanogaster","volume":"112","author":"Sano","year":"2002","journal-title":"Mech. Dev."},{"key":"2021042606411024000_R43","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.cell.2008.12.024","article-title":"The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors","volume":"136","author":"Schwamborn","year":"2009","journal-title":"Cell"},{"key":"2021042606411024000_R44","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.4161\/cc.7.16.6454","article-title":"Lessons from microRNA mutants in worms, flies and mice","volume":"7","author":"Smibert","year":"2008","journal-title":"Cell Cycle"},{"key":"2021042606411024000_R45","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1242\/dev.01026","article-title":"Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary","volume":"131","author":"Song","year":"2004","journal-title":"Development"},{"key":"2021042606411024000_R46","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1101\/gad.13.20.2704","article-title":"Recruitment of Nanos to hunchback mRNA by Pumilio","volume":"13","author":"Sonoda","year":"1999","journal-title":"Genes Dev."},{"key":"2021042606411024000_R47","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1101\/gad.870801","article-title":"Drosophila Brain Tumor is a translational repressor","volume":"15","author":"Sonoda","year":"2001","journal-title":"Genes Dev."},{"key":"2021042606411024000_R48","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.devcel.2005.10.018","article-title":"Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes","volume":"10","author":"Sugimura","year":"2006","journal-title":"Dev. Cell"},{"key":"2021042606411024000_R49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cub.2005.01.005","article-title":"Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation","volume":"15","author":"Szakmary","year":"2005","journal-title":"Curr. Biol."},{"key":"2021042606411024000_R50","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1242\/dev.128.7.1159","article-title":"An autoregulatory feedback loop directs the localized expression of the Drosophila CPEB protein Orb in the developing oocyte","volume":"128","author":"Tan","year":"2001","journal-title":"Development"},{"key":"2021042606411024000_R51","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1242\/dev.050575","article-title":"Drosophila ataxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts","volume":"137","author":"Tastan","year":"2010","journal-title":"Development"},{"key":"2021042606411024000_R52","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1126\/science.1093983","article-title":"Nanos maintains germline stem cell self-renewal by preventing differentiation","volume":"303","author":"Wang","year":"2004","journal-title":"Science"},{"key":"2021042606411024000_R53","doi-asserted-by":"crossref","first-page":"9214","DOI":"10.1073\/pnas.88.20.9214","article-title":"Drosophila 60A gene, another transforming growth factor beta family member, is closely related to human bone morphogenetic proteins","volume":"88","author":"Wharton","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606411024000_R54","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S1097-2765(00)80085-4","article-title":"The Pumilio RNA-binding domain is also a translational regulator","volume":"1","author":"Wharton","year":"1998","journal-title":"Mol. Cell"},{"key":"2021042606411024000_R55","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1242\/dev.124.15.3015","article-title":"Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA","volume":"124","author":"Wreden","year":"1997","journal-title":"Development"},{"key":"2021042606411024000_R56","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.cell.2010.11.022","article-title":"The Fused\/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response","volume":"143","author":"Xia","year":"2010","journal-title":"Cell"},{"key":"2021042606411024000_R57","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0092-8674(00)81424-5","article-title":"decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary","volume":"94","author":"Xie","year":"1998","journal-title":"Cell"},{"key":"2021042606411024000_R58","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1242\/dev.009159","article-title":"Argonaute 1 regulates the fate of germline stem cells in Drosophila","volume":"134","author":"Yang","year":"2007","journal-title":"Development"},{"key":"2021042606411024000_R59","first-page":"1421","article-title":"The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins","volume":"3","author":"Zamore","year":"1997","journal-title":"RNA"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/139\/9\/1547\/1174566\/1547.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/139\/9\/1547\/1174566\/1547.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T09:09:10Z","timestamp":1641460150000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/139\/9\/1547\/45616\/Mei-P26-regulates-the-maintenance-of-ovarian"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,1]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,5,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.077412","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2012,5,1]]}}}