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Although it functions in a variety of processes, the net output of JAK\u2013STAT signalling depends on its spatiotemporal activation, as well as extensive crosstalk with other signalling pathways. <jats:italic>Drosophila<\/jats:italic>, with its relatively simple signal transduction pathways and plethora of genetic analysis tools, is an ideal system for dissecting JAK\u2013STAT signalling interactions. In this review, we explore studies in <jats:italic>Drosophila<\/jats:italic> revealing that JAK\u2013STAT signalling lies at the nexus of a complex network of interlinked pathways, including epidermal growth factor receptor (EGFR), c\u2010Jun N\u2010terminal kinase (JNK), Notch, Insulin, Hippo, bone morphogenetic protein (BMP), Hedgehog (Hh) and Wingless (Wg). These pathways can synergise with or antagonise one another to produce a variety of outcomes. Given the conserved nature of signal transduction pathways, we conclude with our perspective on the implication of JAK\u2013STAT signalling dysregulation in human diseases, and how studies in <jats:italic>Drosophila<\/jats:italic> have the potential to inform and influence clinical research.<\/jats:p>","DOI":"10.1111\/febs.17391","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T12:01:04Z","timestamp":1737028864000},"page":"3298-3320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["What a tangled web we weave: crosstalk between <scp>JAK<\/scp>\u2013<scp>STAT<\/scp> and other signalling pathways during development in <i>Drosophila<\/i>"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-0363","authenticated-orcid":false,"given":"Amartya","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Developmental Biology and Genetics Indian Institute of Science (IISc)  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5116-8668","authenticated-orcid":false,"given":"Chaithra","family":"Anoop","sequence":"additional","affiliation":[{"name":"Department of Biological Science Indian Institute of Science Education and Research (IISER)  Mohali India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-5995","authenticated-orcid":false,"given":"Upendra","family":"Nongthomba","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Genetics Indian Institute of Science (IISc)  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.22580\/iscinotej6.6.1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77422-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb03213.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.4.383"},{"key":"e_1_2_11_6_1","first-page":"923","article-title":"Interferon\u2010dependent transcriptional activation: signal transduction without second messenger involvement?","volume":"2","author":"Levy DE","year":"1990","journal-title":"New Biol"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8555"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90106-M"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7690989"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)89000-9"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.5.1603"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.4.2057"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90105-L"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/366129a0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/366580a0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02411"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.20.3252"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00244-2"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/165.3.1149"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.09.040"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00524-3"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.955202"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.3.300"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81286-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81287-8"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/43206"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00216-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00444041"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(86)90070-9"},{"key":"e_1_2_11_30_1","volume-title":"The genetics of Drosophila","author":"Morgan T. 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