{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:30:54Z","timestamp":1787567454168,"version":"build-2736575974"},"reference-count":62,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"crossref","award":["2020YFA0803502"],"award-info":[{"award-number":["2020YFA0803502"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2020YFA0803502"],"award-info":[{"award-number":["2020YFA0803502"]}],"id":[{"id":"https:\/\/ror.org\/027s68j25","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"crossref","award":["2017YFA0103602"],"award-info":[{"award-number":["2017YFA0103602"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2017YFA0103602"],"award-info":[{"award-number":["2017YFA0103602"]}],"id":[{"id":"https:\/\/ror.org\/027s68j25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Cell-to-cell communication via Delta-Notch signaling is widely used in various tissues and organs to regulate development and patterning; however, the mechanisms regulating Notch signaling for precise cell fate decisions remain poorly understood. Similar to mammals, the intestinal stem cells in the adult\n                    <jats:italic>Drosophila<\/jats:italic>\n                    midgut generate both absorptive and secretory cell progeny, guided by differential levels of Notch activation. Here we performed a forward genetic screen in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and identified glucosylceramide synthase (GlcT), a rate-limiting enzyme for glycosphingolipid (GSL) production, whose mutation causes the development of secretory cell tumors. Genetic analysis of the GSL synthesis pathway, combined with metabolite rescue experiments, revealed that the tumor formation is linked to a deficiency in Mactosylceramide\/Lactosylceramide. This deficiency impaired the endocytic recycling of the Delta, subsequently reducing Notch signaling activation. Conditional knockout of\n                    <jats:italic>Ugcg<\/jats:italic>\n                    , the mammalian ortholog of\n                    <jats:italic>GlcT<\/jats:italic>\n                    , in mouse small intestine caused an excessive differentiation of goblet cells, phenotypes similar to these caused by Notch inhibition. Our study suggests an evolutionarily conserved role for a specific GSL metabolite in modulating Notch signaling during stem cell fate decisions and provides a molecular connection between ceramide metabolism and Notch signaling in regulating tissue homeostasis and tumor formation.\n                  <\/jats:p>","DOI":"10.7554\/elife.106184","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T13:09:43Z","timestamp":1742476183000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.106184","source":"Crossref","is-referenced-by-count":0,"title":["Mac-\/Lactosylceramide regulates intestinal homeostasis and secretory cell fate commitment by facilitating Notch signaling"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3269-4411","authenticated-orcid":true,"given":"Kebei","family":"Tang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"Academy for Advanced Interdisciplinary Studies, Peking University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xuewen","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jiulong","family":"Hu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03j450x81","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Basic Medicine, Nanchang Medical College","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jingyuan","family":"Shi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Yansu","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Chang","family":"Yin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-2859","authenticated-orcid":true,"given":"Fengchao","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5543-1236","authenticated-orcid":true,"given":"Rongwen","family":"Xi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/science.284.5415.770","type":"journal-article","article-title":"Notch signaling: cell fate control and signal integration in development","volume":"284","author":"Artavanis-Tsakonas","year":"1999","journal-title":"Science"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"15318","DOI":"10.1073\/pnas.1202369109","type":"journal-article","article-title":"Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila","volume":"109","author":"Ayukawa","year":"2012","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1242\/dev.114959","type":"journal-article","article-title":"Generation of enteroendocrine cell diversity in midgut stem cell lineages","volume":"142","author":"Beehler-Evans","year":"2015","journal-title":"Development"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1210\/er.2006-0046","type":"journal-article","article-title":"Notch signaling in development and cancer","volume":"28","author":"Bol\u00f3s","year":"2007","journal-title":"Endocrine Reviews"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ceb.2021.05.007","type":"journal-article","article-title":"An amuse-bouche of stem cell regulation: underlying principles and mechanisms from adult Drosophila intestinal stem cells","volume":"73","author":"Boumard","year":"2021","journal-title":"Current Opinion in Cell Biology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1242\/dev.118.2.401","type":"journal-article","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","author":"Brand","year":"1993","journal-title":"Development"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nrm2009","type":"journal-article","article-title":"Notch signalling: a simple pathway becomes complex","volume":"7","author":"Bray","year":"2006","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ceb.2017.12.008","type":"journal-article","article-title":"Notch after cleavage","volume":"51","author":"Bray","year":"2018","journal-title":"Current Opinion in Cell Biology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.ydbio.2007.04.013","type":"journal-article","article-title":"Glycosphingolipids with extended sugar chain have specialized functions in development and behavior of Drosophila","volume":"306","author":"Chen","year":"2007","journal-title":"Developmental Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41556-017-0020-0","type":"journal-article","article-title":"Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells","volume":"20","author":"Chen","year":"2018","journal-title":"Nature Cell Biology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.celrep.2013.10.029","type":"journal-article","article-title":"Structural analysis uncovers lipid-binding properties of Notch ligands","volume":"5","author":"Chillakuri","year":"2013","journal-title":"Cell Reports"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","type":"journal-article","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"9044","DOI":"10.1073\/pnas.1105666108","type":"journal-article","article-title":"Regulation of human EGF receptor by lipids","volume":"108","author":"Coskun","year":"2011","journal-title":"PNAS"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/978-1-4939-1139-4_6","type":"journal-article","article-title":"Antibody uptake assay and in vivo imaging to study intracellular trafficking of Notch and Delta in Drosophila","volume":"1187","author":"Couturier","year":"2014","journal-title":"Methods in Molecular Biology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1038\/emboj.2012.106","type":"journal-article","article-title":"Drosophila midgut homeostasis involves neutral competition between symmetrically dividing intestinal stem cells","volume":"31","author":"de Navascu\u00e9s","year":"2012","journal-title":"The EMBO Journal"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"4737","DOI":"10.1242\/dev.128.23.4737","type":"journal-article","article-title":"Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle in Drosophila follicle cells","volume":"128","author":"Deng","year":"2001","journal-title":"Development"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/gene.20042","type":"journal-article","article-title":"Tissue-specific and inducible Cre-mediated recombination in the gut epithelium","volume":"39","author":"el Marjou","year":"2004","journal-title":"Genesis"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/nature03589","type":"journal-article","article-title":"Notch signals control the fate of immature progenitor cells in the intestine","volume":"435","author":"Fre","year":"2005","journal-title":"Nature"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab0988","type":"journal-article","article-title":"Stem cell regulation. Bidirectional Notch signaling regulates Drosophila intestinal stem cell multipotency","volume":"350","author":"Guo","year":"2015","journal-title":"Science"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34270-0","type":"journal-article","article-title":"A hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila","volume":"13","author":"Guo","year":"2022","journal-title":"Nature Communications"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1083\/jcb.200907116","type":"journal-article","article-title":"Notch ligand activity is modulated by glycosphingolipid membrane composition in Drosophila melanogaster","volume":"188","author":"Hamel","year":"2010","journal-title":"The Journal of Cell Biology"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1242\/dev.172148","type":"journal-article","article-title":"Mechanisms of Notch signaling: a simple logic deployed in time and space","volume":"146","author":"Henrique","year":"2019","journal-title":"Development"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/glycob\/cwg094","type":"journal-article","article-title":"The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity","volume":"13","author":"Ideo","year":"2003","journal-title":"Glycobiology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"32598","DOI":"10.1074\/jbc.M112.371005","type":"journal-article","article-title":"Glycosphingolipids are essential for intestinal endocytic function","volume":"287","author":"Jennemann","year":"2012","journal-title":"The Journal of Biological Chemistry"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1016\/j.cell.2009.05.014","type":"journal-article","article-title":"Cytokine\/Jak\/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut","volume":"137","author":"Jiang","year":"2009","journal-title":"Cell"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.stem.2010.11.026","type":"journal-article","article-title":"EGFR\/Ras\/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila","volume":"8","author":"Jiang","year":"2011","journal-title":"Cell Stem Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1242\/dev.080614","type":"journal-article","article-title":"Stem cells living with a Notch","volume":"140","author":"Koch","year":"2013","journal-title":"Development"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.cell.2009.03.045","type":"journal-article","article-title":"The canonical Notch signaling pathway: unfolding the activation mechanism","volume":"137","author":"Kopan","year":"2009","journal-title":"Cell"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1093\/bioinformatics\/bty648","type":"journal-article","article-title":"Scaling read aligners to hundreds of threads on general-purpose processors","volume":"35","author":"Langmead","year":"2019","journal-title":"Bioinformatics"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/s0896-6273(00)80701-1","type":"journal-article","article-title":"Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis","volume":"22","author":"Lee","year":"1999","journal-title":"Neuron"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/nature07329","type":"journal-article","article-title":"Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells","volume":"455","author":"Lin","year":"2008","journal-title":"Nature"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1101\/gad.200901","type":"journal-article","article-title":"Delta signaling from the germ line controls the proliferation and differentiation of the somatic follicle cells during Drosophila oogenesis","volume":"15","author":"L\u00f3pez-Schier","year":"2001","journal-title":"Genes & Development"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202152729","type":"journal-article","article-title":"The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling","volume":"22","author":"Martins","year":"2021","journal-title":"EMBO Reports"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2202004pl6","type":"journal-article","article-title":"Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila","volume":"2004","author":"McGuire","year":"2004","journal-title":"Science\u2019s STKE"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","type":"journal-article","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Research"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1242\/dev.124.8.1485","type":"journal-article","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":"Micchelli","year":"1997","journal-title":"Development"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nature04371","type":"journal-article","article-title":"Evidence that stem cells reside in the adult Drosophila midgut epithelium","volume":"439","author":"Micchelli","year":"2006","journal-title":"Nature"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"32417","DOI":"10.1074\/jbc.C200381200","type":"journal-article","article-title":"The Drosophila melanogaster brainiac protein is a glycolipid-specific beta 1,3N-acetylglucosaminyltransferase","volume":"277","author":"M\u00fcller","year":"2002","journal-title":"The Journal of Biological Chemistry"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.devcel.2018.08.013","type":"journal-article","article-title":"Dietary lipids modulate notch signaling and influence adult intestinal development and metabolism in Drosophila","volume":"47","author":"Obniski","year":"2018","journal-title":"Developmental Cell"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature04333","type":"journal-article","article-title":"The adult Drosophila posterior midgut is maintained by pluripotent stem cells","volume":"439","author":"Ohlstein","year":"2006","journal-title":"Nature"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1126\/science.1136606","type":"journal-article","article-title":"Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling","volume":"315","author":"Ohlstein","year":"2007","journal-title":"Science"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.bbagen.2012.04.008","type":"journal-article","article-title":"Globoside promotes activation of ERK by interaction with the epidermal growth factor receptor","volume":"1820","author":"Park","year":"2012","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1038\/ncb3214","type":"journal-article","article-title":"Niche appropriation by Drosophila intestinal stem cell tumours","volume":"17","author":"Patel","year":"2015","journal-title":"Nature Cell Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.semcdb.2012.01.010","type":"journal-article","article-title":"Notch signaling in human development and disease","volume":"23","author":"Penton","year":"2012","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"4585","DOI":"10.1242\/dev.065292","type":"journal-article","article-title":"Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine","volume":"138","author":"Perdigoto","year":"2011","journal-title":"Development"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"R471","DOI":"10.1016\/s0960-9822(00)00577-7","type":"journal-article","article-title":"Mastermind is a putative activator for Notch","volume":"10","author":"Petcherski","year":"2000","journal-title":"Current Biology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/embor.2008.7","type":"journal-article","article-title":"Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2","volume":"9","author":"Riccio","year":"2008","journal-title":"EMBO Reports"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.devcel.2004.08.019","type":"journal-article","article-title":"Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways","volume":"7","author":"Ryoo","year":"2004","journal-title":"Developmental Cell"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1242\/dev.02811","type":"journal-article","article-title":"The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila","volume":"134","author":"Sasamura","year":"2007","journal-title":"Development"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1242\/dev.083683","type":"journal-article","article-title":"GPI biosynthesis is essential for rhodopsin sorting at the trans-Golgi network in Drosophila photoreceptors","volume":"140","author":"Satoh","year":"2013","journal-title":"Development"},{"key":"bib51","first-page":"1233","type":"journal-article","article-title":"Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer","volume":"61","author":"Selzner","year":"2001","journal-title":"Cancer Research"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/35036052","type":"journal-article","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s10719-007-9069-5","type":"journal-article","article-title":"Distinct contributions of beta 4GalNAcTA and beta 4GalNAcTB to Drosophila glycosphingolipid biosynthesis","volume":"25","author":"Stolz","year":"2008","journal-title":"Glycoconjugate Journal"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.15252\/embj.201796632","type":"journal-article","article-title":"Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands","volume":"36","author":"Suckling","year":"2017","journal-title":"The EMBO Journal"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1242\/dev.070763","type":"journal-article","article-title":"Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells","volume":"139","author":"VanDussen","year":"2012","journal-title":"Development"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/nature03659","type":"journal-article","article-title":"Notch\/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells","volume":"435","author":"van Es","year":"2005","journal-title":"Nature"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"4858","DOI":"10.1074\/jbc.C400571200","type":"journal-article","article-title":"Egghead and brainiac are essential for glycosphingolipid biosynthesis in vivo","volume":"280","author":"Wandall","year":"2005","journal-title":"The Journal of Biological Chemistry"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1242\/dev.123208","type":"journal-article","article-title":"Ttk69 acts as a master repressor of enteroendocrine cell specification in Drosophila intestinal stem cell lineages","volume":"142","author":"Wang","year":"2015","journal-title":"Development"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ydbio.2011.03.018","type":"journal-article","article-title":"EGFR, Wingless and JAK\/STAT signaling cooperatively maintain Drosophila intestinal stem cells","volume":"354","author":"Xu","year":"2011","journal-title":"Developmental Biology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0070-2153(10)92005-X","type":"journal-article","article-title":"Endocytosis and intracellular trafficking of Notch and its ligands","volume":"92","author":"Yamamoto","year":"2010","journal-title":"Current Topics in Developmental Biology"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.stemcr.2017.11.014","type":"journal-article","article-title":"A phyllopod-mediated feedback loop promotes intestinal stem cell enteroendocrine commitment in Drosophila","volume":"10","author":"Yin","year":"2018","journal-title":"Stem Cell Reports"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/dvg.20661","type":"journal-article","article-title":"Characterization of midgut stem cell- and enteroblast-specific Gal4 lines in Drosophila","volume":"48","author":"Zeng","year":"2010","journal-title":"Genesis"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/106184\/elife-106184-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/106184\/elife-106184-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/106184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:15:03Z","timestamp":1787562903000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/106184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,23]]},"references-count":62,"alternative-id":["10.7554\/eLife.106184"],"URL":"https:\/\/doi.org\/10.7554\/elife.106184","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.02.04.636335","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.106184.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.106184.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.106184.2","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,23]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP106184"}}