{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:13:34Z","timestamp":1778868814592,"version":"3.51.4"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n The\n Drosophila<\/jats:italic>\n gene\n uninflatable<\/jats:italic>\n (\n uif<\/jats:italic>\n ) encodes a conserved insect protein, first identified for its roles in the development and endopolyploid growth of several larval tissues. Uif is a transmembrane protein and its large extracellular domain contains several protein-protein interaction motifs, including multiple EGF (\n E<\/jats:bold>\n pidermal\n G<\/jats:bold>\n rowth\n F<\/jats:bold>\n actor-like) repeats. More recent studies have established that Uif can interact with Notch, a major regulator of\n Drosophila<\/jats:italic>\n growth and differentiation, through its EGF repeats and have identified ways that Uif binding can modify Notch behavior. Endocytosis of Notch-Uif complexes into a particular class of endosomes has also been identified and implicated in cell fate decisions in the sense organs of the notum (thorax). We have examined\n uif\u2019s<\/jats:italic>\n functions in the\n Drosophila<\/jats:italic>\n wing to assess possible roles in 1) growth of a mitotically derived tissue, 2) cell fate decisions in specialized wing structures, and 3)\n Notch<\/jats:italic>\n -dependent processes. We used previously characterized Gal4 lines and RNAi constructs to suppress\n uif<\/jats:italic>\n and\n Notch<\/jats:italic>\n in different wing compartments. In addition to a role in mitotic growth throughout the wing, we have identified two new\n uif<\/jats:italic>\n activities that are also shared with\n Notch<\/jats:italic>\n : 1) regulation of pigment synthesis within the wing cuticle and 2) control of chemosensory sense organ number in the anterior wing margin through a role in an apoptosis-related mechanism. However,\n uif<\/jats:italic>\n does not participate in two roles of\n Notch<\/jats:italic>\n that regulate cell fate decisions: sense organ differentiation and formation of wing vein tissue. Given the similarities in the development of the notal and wing margin sense organs, we investigated further the previously proposed role for\n uif<\/jats:italic>\n in differentiation of these structures on the notum. We found that loss of\n uif<\/jats:italic>\n affects the growth of the bristles of the notal microchaete sense organs, but not their differentiation.\n <\/jats:p>","DOI":"10.1371\/journal.pone.0344871","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:42:26Z","timestamp":1778866946000},"page":"e0344871","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functions of Uninflatable in the Drosophila melanogaster wing and notum"],"prefix":"10.1371","volume":"21","author":[{"given":"Taylor","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliet E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura J.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian C.","family":"Sy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Karki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4095-541X","authenticated-orcid":true,"given":"Manshi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seniha","family":"Elcik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1585-196X","authenticated-orcid":true,"given":"Kathleen 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Noorolyai","year":"2019","journal-title":"Gene"},{"issue":"9","key":"pone.0344871.ref004","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41580-023-00591-1","article-title":"Cellular and molecular mechanisms of Hedgehog signalling","volume":"24","author":"Y Zhang","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"18","key":"pone.0344871.ref005","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1016\/j.cub.2014.07.054","article-title":"Uninflatable and Notch control the targeting of Sara endosomes during asymmetric division","volume":"24","author":"S Loub\u00e9ry","year":"2014","journal-title":"Curr Biol"},{"issue":"3","key":"pone.0344871.ref006","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.devcel.2009.01.002","article-title":"Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger\/TNF signaling in Drosophila","volume":"16","author":"T Igaki","year":"2009","journal-title":"Dev 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A"},{"issue":"6","key":"pone.0344871.ref010","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1073\/pnas.040576497","article-title":"Notch signaling directly controls cell proliferation in the Drosophila wing disc","volume":"97","author":"A Baonza","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0344871.ref011","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1242\/dev.107.2.389","article-title":"Development of adult sensilla on the wing and notum of Drosophila melanogaster","volume":"107","author":"V Hartenstein","year":"1989","journal-title":"Development"},{"issue":"1","key":"pone.0344871.ref012","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0012-1606(90)90147-B","article-title":"A dual function of the Notch gene in Drosophila sensillum development","volume":"142","author":"V Hartenstein","year":"1990","journal-title":"Dev Biol"},{"key":"pone.0344871.ref013","doi-asserted-by":"crossref","unstructured":"Giraldez 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Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. 2003.","DOI":"10.1242\/dev.00904"},{"issue":"1","key":"pone.0344871.ref014","first-page":"359","article-title":"Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc","volume":"122","author":"JF de Celis","year":"1996","journal-title":"Development"},{"issue":"2","key":"pone.0344871.ref015","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ydbio.2009.09.040","article-title":"uninflatable encodes a novel ectodermal apical surface protein required for tracheal inflation in Drosophila","volume":"336","author":"L Zhang","year":"2009","journal-title":"Dev Biol"},{"issue":"4","key":"pone.0344871.ref016","article-title":"Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila","volume":"7","author":"G Xie","year":"2012","journal-title":"PLoS 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Sci"},{"issue":"1","key":"pone.0344871.ref020","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/j.1460-2075.1994.tb06236.x","article-title":"The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development","volume":"13","author":"J Capdevila","year":"1994","journal-title":"EMBO J"},{"issue":"4","key":"pone.0344871.ref021","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0040-8166(87)90044-9","article-title":"The final stages of wing development in Drosophila melanogaster","volume":"19","author":"SA Johnson","year":"1987","journal-title":"Tissue Cell"},{"issue":"1","key":"pone.0344871.ref022","doi-asserted-by":"crossref","first-page":"10577","DOI":"10.1038\/s41467-024-54527-0","article-title":"Mechanics of Drosophila wing deployment","volume":"15","author":"S Hadjaje","year":"2024","journal-title":"Nat 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Huppert","year":"1997","journal-title":"Development"},{"issue":"1","key":"pone.0344871.ref026","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0092-8674(94)90174-0","article-title":"The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes","volume":"76","author":"U Hinz","year":"1994","journal-title":"Cell"},{"issue":"1","key":"pone.0344871.ref027","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12861-020-00217-1","article-title":"Wingless and Archipelago, a fly E3 ubiquitin ligase and a homolog of human tumor suppressor FBW7, show an antagonistic relationship in wing development","volume":"20","author":"S Nam","year":"2020","journal-title":"BMC Dev Biol"},{"issue":"5375","key":"pone.0344871.ref028","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.281.5375.409","article-title":"Boundary formation in Drosophila wing: Notch activity attenuated by the POU protein Nubbin","volume":"281","author":"CJ Neumann","year":"1998","journal-title":"Science"},{"issue":"8","key":"pone.0344871.ref029","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1242\/dev.124.8.1485","article-title":"The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate","volume":"124","author":"CA Micchelli","year":"1997","journal-title":"Development"},{"issue":"2","key":"pone.0344871.ref030","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1242\/dev.117.2.441","article-title":"Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila","volume":"117","author":"K Blochlinger","year":"1993","journal-title":"Development"},{"issue":"10","key":"pone.0344871.ref031","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1046\/j.1365-2443.2001.00473.x","article-title":"Over-expression of DREF in the Drosophila wing imaginal 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Pinot","year":"2024","journal-title":"Cells"},{"issue":"1","key":"pone.0344871.ref034","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1242\/dev.056309","article-title":"Megalin-dependent yellow endocytosis restricts melanization in the Drosophila cuticle","volume":"138","author":"F Riedel","year":"2011","journal-title":"Development"},{"issue":"4","key":"pone.0344871.ref035","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nrm778","article-title":"Megalin and cubilin: Multifunctional endocytic receptors","volume":"3","author":"EI Christensen","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"24","key":"pone.0344871.ref036","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1242\/dev.041392","article-title":"Patched regulates Smoothened trafficking using lipoprotein-derived lipids","volume":"136","author":"H Khaliullina","year":"2009","journal-title":"Development"},{"issue":"2","key":"pone.0344871.ref037","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ydbio.2011.07.007","article-title":"Cell death and selective adhesion reorganize the dorsoventral boundary for zigzag patterning of Drosophila wing margin hairs","volume":"357","author":"M Takemura","year":"2011","journal-title":"Dev Biol"},{"issue":"18","key":"pone.0344871.ref038","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1242\/dev.127.18.3971","article-title":"Generation of medial and lateral dorsal body domains by the pannier gene of Drosophila","volume":"127","author":"M Calleja","year":"2000","journal-title":"Development"},{"key":"pone.0344871.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-1139-4_1","article-title":"Introduction to Notch signaling","volume":"1187","author":"S Yamamoto","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"6","key":"pone.0344871.ref040","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1242\/dev.120.6.1433","article-title":"Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis","volume":"120","author":"F Schweisguth","year":"1994","journal-title":"Development"},{"issue":"9","key":"pone.0344871.ref041","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1101\/gad.6.9.1752","article-title":"The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development","volume":"6","author":"AG Bang","year":"1992","journal-title":"Genes Dev"},{"issue":"4","key":"pone.0344871.ref042","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.cub.2011.01.015","article-title":"Apoptosis ensures spacing pattern formation of Drosophila sensory organs","volume":"21","author":"A Koto","year":"2011","journal-title":"Curr 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Drosophila spermatid individualization","volume":"2","author":"JR Huh","year":"2004","journal-title":"PLoS Biol"},{"key":"pone.0344871.ref047","doi-asserted-by":"crossref","first-page":"1184041","DOI":"10.3389\/fceld.2023.1184041","article-title":"Non-lethal roles of the initiator caspase Dronc in Drosophila","volume":"2","author":"D Dominguez","year":"2023","journal-title":"Frontiers in Cell Death"},{"issue":"5","key":"pone.0344871.ref048","article-title":"Chemosensory sensilla of the Drosophila wing express a candidate ionotropic pheromone receptor","volume":"17","author":"Z He","year":"2019","journal-title":"PLoS Biol"},{"key":"pone.0344871.ref049","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3389\/fnbeh.2014.00254","article-title":"Hygienic grooming is induced by contact chemicals in Drosophila melanogaster","volume":"8","author":"A Yanagawa","year":"2014","journal-title":"Front Behav Neurosci"}],"container-title":["PLOS 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