{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:39:01Z","timestamp":1772156341132,"version":"3.50.1"},"posted":{"date-parts":[[2023,3,15]]},"group-title":"Developmental Biology","reference-count":86,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Separate tissues connect through adjoining basement membranes to carry out molecular barrier, exchange, and organ support functions. Cell adhesion at these connections must be robust and balanced to withstand independent tissue movement. Yet, how cells achieve synchronized adhesion to connect tissues is unknown. Here, we have investigated this question using the\n                  <jats:italic>C. elegans<\/jats:italic>\n                  utse-seam tissue connection that supports the uterus during egg-laying. Through genetics, quantitative fluorescence, and cell specific molecular disruption, we show that type IV collagen, which fastens the linkage, also activates the collagen receptor discoidin domain receptor 2 (DDR-2) in both the utse and seam. RNAi depletion, genome editing, and photobleaching experiments revealed that DDR-2 signals through LET-60\/Ras to coordinately strengthen an integrin adhesion in the utse and seam that stabilizes their connection. These results uncover a synchronizing mechanism for robust adhesion during tissue connection, where collagen both affixes the linkage and signals to both tissues to bolster their adhesion.\n                <\/jats:p>","DOI":"10.1101\/2023.03.14.532639","type":"posted-content","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T11:30:13Z","timestamp":1678879813000},"source":"Crossref","is-referenced-by-count":0,"title":["Reciprocal discoidin domain receptor signaling strengthens integrin adhesion to connect adjacent tissues"],"prefix":"10.64898","author":[{"given":"Kieop","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-0337","authenticated-orcid":false,"given":"Ranjay","family":"Jayadev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara G.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel W.","family":"Kenny-Ganzert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyi","family":"Chi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Ramos-Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddharthan Balachandar","family":"Thendral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-6917","authenticated-orcid":false,"given":"David R.","family":"Sherwood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023051911401169000_2023.03.14.532639v2.1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.100.6.1988"},{"key":"2023051911401169000_2023.03.14.532639v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2010.06.010"},{"key":"2023051911401169000_2023.03.14.532639v2.3","doi-asserted-by":"crossref","unstructured":"Bayer, S. V. , W. R. Grither , A. Brenot , P. Y. Hwang , C. E. Barcus , M. Ernst , P. Pence , C. Walter , A. Pathak and G. D. Longmore (2019). \"DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs.\" Elife 8.","DOI":"10.7554\/eLife.45508"},{"key":"2023051911401169000_2023.03.14.532639v2.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2511-3"},{"key":"2023051911401169000_2023.03.14.532639v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07976-3"},{"key":"2023051911401169000_2023.03.14.532639v2.6","doi-asserted-by":"crossref","first-page":"836797","DOI":"10.3389\/fcell.2022.836797","article-title":"The Collagen Receptor Discoidin Domain Receptor 1b Enhances Integrin beta1-Mediated Cell Migration by Interacting With Talin and Promoting Rac1 Activation","volume":"10","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.12.002"},{"key":"2023051911401169000_2023.03.14.532639v2.8"},{"key":"2023051911401169000_2023.03.14.532639v2.9","first-page":"12","article-title":"Extracellular matrix in development: insights from mechanisms conserved between invertebrates and vertebrates","volume":"3","year":"2011","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000907"},{"key":"2023051911401169000_2023.03.14.532639v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2010.07.004"},{"key":"2023051911401169000_2023.03.14.532639v2.12","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-7-30"},{"key":"2023051911401169000_2023.03.14.532639v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.09.014"},{"key":"2023051911401169000_2023.03.14.532639v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.01.038"},{"key":"2023051911401169000_2023.03.14.532639v2.15","doi-asserted-by":"crossref","first-page":"747314","DOI":"10.3389\/fcell.2021.747314","article-title":"Recent Advances in the Role of Discoidin Domain Receptor Tyrosine Kinase 1 and Discoidin Domain Receptor Tyrosine Kinase 2 in Breast and Ovarian Cancer","volume":"9","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2015.08.001"},{"key":"2023051911401169000_2023.03.14.532639v2.17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-14"},{"key":"2023051911401169000_2023.03.14.532639v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53176-4"},{"key":"2023051911401169000_2023.03.14.532639v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2641"},{"key":"2023051911401169000_2023.03.14.532639v2.20","doi-asserted-by":"crossref","unstructured":"Edelstein, A. , N. Amodaj , K. Hoover , R. Vale and N. Stuurman (2010). \"Computer control of microscopes using microManager.\" Curr Protoc Mol Biol Chapter 14: Unit14 20.","DOI":"10.1002\/0471142727.mb1420s92"},{"key":"2023051911401169000_2023.03.14.532639v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.06.023"},{"key":"2023051911401169000_2023.03.14.532639v2.22","first-page":"7","article-title":"The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution","volume":"131","year":"2018","journal-title":"J Cell Sci"},{"key":"2023051911401169000_2023.03.14.532639v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601922"},{"key":"2023051911401169000_2023.03.14.532639v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1865"},{"key":"2023051911401169000_2023.03.14.532639v2.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.444158"},{"key":"2023051911401169000_2023.03.14.532639v2.26","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600870R"},{"key":"2023051911401169000_2023.03.14.532639v2.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.09.028"},{"key":"2023051911401169000_2023.03.14.532639v2.28","first-page":"1","article-title":"Hemicentin-mediated type IV collagen assembly strengthens juxtaposed basement membrane linkage","volume":"222","year":"2023","journal-title":"J Cell Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.29","doi-asserted-by":"publisher","DOI":"10.1895\/wormbook.1.181.1"},{"key":"2023051911401169000_2023.03.14.532639v2.30","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017459"},{"key":"2023051911401169000_2023.03.14.532639v2.31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00712.x"},{"key":"2023051911401169000_2023.03.14.532639v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.06.006"},{"key":"2023051911401169000_2023.03.14.532639v2.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006475"},{"key":"2023051911401169000_2023.03.14.532639v2.34","doi-asserted-by":"publisher","DOI":"10.4161\/cam.21831"},{"key":"2023051911401169000_2023.03.14.532639v2.35","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201903124"},{"issue":"20","key":"2023051911401169000_2023.03.14.532639v2.36","doi-asserted-by":"crossref","first-page":"eabn2265","DOI":"10.1126\/sciadv.abn2265","article-title":"A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations","volume":"8","author":"C. Genomics England Research","year":"2022","journal-title":"Sci Adv"},{"key":"2023051911401169000_2023.03.14.532639v2.37"},{"key":"2023051911401169000_2023.03.14.532639v2.38","doi-asserted-by":"crossref","unstructured":"Juskaite, V. , D. S. Corcoran and B. Leitinger (2017). \"Collagen induces activation of DDR1 through lateral dimer association and phosphorylation between dimers.\" Elife 6.","DOI":"10.7554\/eLife.25716"},{"key":"2023051911401169000_2023.03.14.532639v2.39","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(03)00050-1"},{"key":"2023051911401169000_2023.03.14.532639v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.05.022"},{"issue":"76","key":"2023051911401169000_2023.03.14.532639v2.41","first-page":"58","article-title":"Tissue linkage through adjoining basement membranes: The long and the short term of it","volume":"75","year":"2019","journal-title":"Matrix Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.12.018"},{"key":"2023051911401169000_2023.03.14.532639v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.093"},{"key":"2023051911401169000_2023.03.14.532639v2.44","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20564"},{"key":"2023051911401169000_2023.03.14.532639v2.45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105795200"},{"key":"2023051911401169000_2023.03.14.532639v2.46","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800180-6.00002-5"},{"key":"2023051911401169000_2023.03.14.532639v2.47","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3487"},{"key":"2023051911401169000_2023.03.14.532639v2.48","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.6.729"},{"key":"2023051911401169000_2023.03.14.532639v2.49","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200409000-00020"},{"key":"2023051911401169000_2023.03.14.532639v2.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.10.067"},{"key":"2023051911401169000_2023.03.14.532639v2.51","doi-asserted-by":"crossref","unstructured":"Moerman, D. G. and B. D. Williams (2006). \"Sarcomere assembly in C. elegans muscle.\" WormBook: 1\u201316.","DOI":"10.1895\/wormbook.1.81.1"},{"key":"2023051911401169000_2023.03.14.532639v2.52","doi-asserted-by":"publisher","DOI":"10.1186\/s12861-015-0076-7"},{"key":"2023051911401169000_2023.03.14.532639v2.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.08.024"},{"key":"2023051911401169000_2023.03.14.532639v2.54","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.168021"},{"key":"2023051911401169000_2023.03.14.532639v2.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906541106"},{"key":"2023051911401169000_2023.03.14.532639v2.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-020-0329-y"},{"issue":"11","key":"2023051911401169000_2023.03.14.532639v2.57","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1242\/dev.122.11.3617","article-title":"Morphogenesis of the C. elegans hermaphrodite uterus","volume":"122","year":"1996","journal-title":"Development"},{"key":"2023051911401169000_2023.03.14.532639v2.58","doi-asserted-by":"crossref","unstructured":"Pani, A. M. and B. Goldstein (2018). \"Direct visualization of a native Wnt in vivo reveals that a long-range Wnt gradient forms by extracellular dispersal.\" Elife 7.","DOI":"10.7554\/eLife.38325"},{"key":"2023051911401169000_2023.03.14.532639v2.59","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1471-213X-10-14","article-title":"Characterization of the astacin family of metalloproteases in C. elegans","volume":"10","year":"2010","journal-title":"BMC Dev Biol"},{"key":"2023051911401169000_2023.03.14.532639v2.60","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000164"},{"key":"2023051911401169000_2023.03.14.532639v2.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.12.009"},{"key":"2023051911401169000_2023.03.14.532639v2.62","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2505604"},{"key":"2023051911401169000_2023.03.14.532639v2.63","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.110"},{"key":"2023051911401169000_2023.03.14.532639v2.64","doi-asserted-by":"crossref","unstructured":"Sato, K. , A. Norris , M. Sato and B. D. Grant (2014). \"C. elegans as a model for membrane traffic.\" WormBook: 1\u201347.","DOI":"10.1895\/wormbook.1.77.2"},{"key":"2023051911401169000_2023.03.14.532639v2.65","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023051911401169000_2023.03.14.532639v2.66","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00168-0"},{"key":"2023051911401169000_2023.03.14.532639v2.67","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.18.2251"},{"key":"2023051911401169000_2023.03.14.532639v2.68","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.5.933"},{"key":"2023051911401169000_2023.03.14.532639v2.69","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20135090"},{"key":"2023051911401169000_2023.03.14.532639v2.70","doi-asserted-by":"crossref","unstructured":"Stiernagle, T . (2006). \"Maintenance of C. elegans.\" WormBook: 1\u201311.","DOI":"10.1895\/wormbook.1.101.1"},{"key":"2023051911401169000_2023.03.14.532639v2.71","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01149"},{"key":"2023051911401169000_2023.03.14.532639v2.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.03.003"},{"key":"2023051911401169000_2023.03.14.532639v2.73","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00579-5"},{"key":"2023051911401169000_2023.03.14.532639v2.74","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1981.tb05690.x"},{"key":"2023051911401169000_2023.03.14.532639v2.75","doi-asserted-by":"publisher","DOI":"10.1186\/s12862-015-0554-3"},{"key":"2023051911401169000_2023.03.14.532639v2.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.11.001"},{"key":"2023051911401169000_2023.03.14.532639v2.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.02.002"},{"key":"2023051911401169000_2023.03.14.532639v2.78","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.6.883"},{"key":"2023051911401169000_2023.03.14.532639v2.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.02.012"},{"issue":"1","key":"2023051911401169000_2023.03.14.532639v2.80","doi-asserted-by":"crossref","first-page":"e1006592","DOI":"10.1371\/journal.pgen.1006592","article-title":"beta-Integrin de-phosphorylation by the Density-Enhanced Phosphatase DEP-1 attenuates EGFR signaling in C. elegans","volume":"13","year":"2017","journal-title":"PLoS Genet"},{"key":"2023051911401169000_2023.03.14.532639v2.81","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96824-4"},{"key":"2023051911401169000_2023.03.14.532639v2.82","doi-asserted-by":"publisher","DOI":"10.1242\/dev.066431"},{"issue":"5","key":"2023051911401169000_2023.03.14.532639v2.83","doi-asserted-by":"crossref","first-page":"e1005249","DOI":"10.1371\/journal.pgen.1005249","article-title":"Minor Type IV Collagen alpha5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1","volume":"11","year":"2015","journal-title":"PLoS Genet"},{"key":"2023051911401169000_2023.03.14.532639v2.84","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052209"},{"key":"2023051911401169000_2023.03.14.532639v2.85","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00701"},{"key":"2023051911401169000_2023.03.14.532639v2.86","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81082-X"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.03.14.532639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:24:51Z","timestamp":1768451091000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.03.14.532639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":86,"URL":"https:\/\/doi.org\/10.1101\/2023.03.14.532639","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.7554\/eLife.87037.3","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.87037.3","asserted-by":"object"}],"has-version":[{"id-type":"doi","id":"10.7554\/eLife.87037.1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.87037.2","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2023,3,15]]},"subtype":"preprint"}}