{"year":"2022","acknowledged_ssus":[{"_id":"LifeSc"}],"project":[{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800"}],"ddc":["570"],"file_date_updated":"2023-04-21T22:30:03Z","publication_identifier":{"issn":["2663-337X"]},"author":[{"first_name":"Stephanie","last_name":"Wachner","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","full_name":"Wachner, Stephanie"}],"has_accepted_license":"1","page":"170","doi":"10.15479/at:ista:11193","_id":"11193","language":[{"iso":"eng"}],"citation":{"apa":"Wachner, S. (2022). <i>Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>","ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>.","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022.","mla":"Wachner, Stephanie. <i>Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>.","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022."},"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","oa":1,"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_created":"2022-04-20T08:59:07Z","alternative_title":["ISTA Thesis"],"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","status":"public","related_material":{"record":[{"id":"10614","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"544"}]},"month":"04","supervisor":[{"orcid":"0000-0001-8323-8353","last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","date_updated":"2023-09-19T10:15:54Z","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"type":"dissertation","file":[{"relation":"main_file","checksum":"999ab16884c4522486136ebc5ae8dbff","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","embargo":"2023-04-20","creator":"cchlebak","access_level":"open_access","content_type":"application/pdf","date_updated":"2023-04-21T22:30:03Z","file_size":8820951,"date_created":"2022-04-20T09:03:57Z","file_id":"11195"},{"date_updated":"2023-04-21T22:30:03Z","file_id":"11329","file_size":65864612,"date_created":"2022-04-22T12:41:00Z","checksum":"fd92b1e38d53bdf8b458213882d41383","relation":"source_file","content_type":"application/x-zip-compressed","creator":"cchlebak","embargo_to":"open_access","access_level":"closed","file_name":"Thesis_Stephanie_Wachner_20200414.zip"}],"day":"20","degree_awarded":"PhD","department":[{"_id":"GradSch"},{"_id":"DaSi"}],"abstract":[{"lang":"eng","text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident\r\nmacrophages and responses to infections and tumors. However, the mechanisms immune\r\ncells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue barrier of the germband in the embryo. One strategy is the strengthening\r\nof the actin cortex through developmentally controlled transcriptional regulation induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes to overcome the physical resistance of the surrounding tissue and\r\ntranslocate their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion process is the initial step of the leading hemocytes entering\r\nthe tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis suggests that there might be different mechanisms controlling immune cell migration\r\nwithin the confined environment in vivo, one of these being the general ability to overcome\r\nthe resistance of the surrounding tissue and another affecting the order of hemocytes that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether, my findings provide deeper insights into transcriptional changes in immune\r\ncells that enable efficient tissue invasion and pave the way for future studies investigating the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover, they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point toward a potentially\r\nconserved role for canonical BMP signaling in specifying immune cells that lead the migration\r\nof tissue resident macrophages during embryogenesis."}],"date_published":"2022-04-20T00:00:00Z","publication_status":"published"}