[{"day":"20","article_processing_charge":"No","has_accepted_license":"1","page":"170","citation":{"chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11193.","mla":"Wachner, Stephanie. Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11193.","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022.","ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","apa":"Wachner, S. (2022). Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11193","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:10.15479/at:ista:11193"},"date_published":"2022-04-20T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","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."}],"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","status":"public","ddc":["570"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"11193","file":[{"relation":"main_file","file_id":"11195","embargo":"2023-04-20","date_created":"2022-04-20T09:03:57Z","date_updated":"2023-04-21T22:30:03Z","checksum":"999ab16884c4522486136ebc5ae8dbff","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","access_level":"open_access","content_type":"application/pdf","file_size":8820951,"creator":"cchlebak"},{"file_id":"11329","relation":"source_file","checksum":"fd92b1e38d53bdf8b458213882d41383","date_updated":"2023-04-21T22:30:03Z","date_created":"2022-04-22T12:41:00Z","access_level":"closed","file_name":"Thesis_Stephanie_Wachner_20200414.zip","embargo_to":"open_access","creator":"cchlebak","file_size":65864612,"content_type":"application/x-zip-compressed"}],"oa_version":"Published Version","month":"04","publication_identifier":{"issn":["2663-337X"]},"project":[{"name":"Tissue barrier penetration is crucial for immunity and metastasis","_id":"26199CA4-B435-11E9-9278-68D0E5697425","grant_number":"24800"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"LifeSc"}],"supervisor":[{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11193","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2023-04-21T22:30:03Z","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","year":"2022","date_updated":"2023-09-19T10:15:54Z","date_created":"2022-04-20T08:59:07Z","author":[{"id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","last_name":"Wachner","first_name":"Stephanie","full_name":"Wachner, Stephanie"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"10614"},{"relation":"part_of_dissertation","status":"public","id":"544"}]}},{"publication_identifier":{"issn":["2663-337X"]},"month":"12","oa":1,"doi":"10.15479/AT:ISTA:8983","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"CampIT"}],"file_date_updated":"2021-12-31T23:30:04Z","acknowledgement":"Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria.","year":"2020","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"8557"},{"relation":"part_of_dissertation","status":"public","id":"6187"}]},"author":[{"full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938","first_name":"Shamsi","last_name":"Emtenani"}],"date_created":"2020-12-30T15:41:26Z","date_updated":"2023-09-07T13:24:17Z","has_accepted_license":"1","article_processing_charge":"No","day":"30","citation":{"ama":"Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983","apa":"Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983","ieee":"S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020.","ista":"Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria.","short":"S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020.","mla":"Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.","chicago":"Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983."},"page":"141","date_published":"2020-12-30T00:00:00Z","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers.","lang":"eng"}],"_id":"8983","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"title":"Metabolic regulation of Drosophila macrophage tissue invasion","status":"public","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":10848175,"creator":"semtenan","access_level":"open_access","file_name":"Thesis_Shamsi_Emtenani_pdfA.pdf","checksum":"ec2797ab7a6f253b35df0572b36d1b43","date_updated":"2021-12-31T23:30:04Z","date_created":"2020-12-30T15:34:01Z","relation":"main_file","file_id":"8984","embargo":"2021-12-30"},{"date_updated":"2021-12-31T23:30:04Z","date_created":"2020-12-30T15:37:36Z","checksum":"cc30e6608a9815414024cf548dff3b3a","relation":"source_file","file_id":"8985","file_size":10073648,"content_type":"application/pdf","creator":"semtenan","embargo_to":"open_access","file_name":"Thesis_Shamsi_Emtenani_source file.pdf","access_level":"closed"}]},{"abstract":[{"text":"Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","file":[{"access_level":"closed","embargo_to":"open_access","file_name":"Katarina Valoskova_PhD thesis_final version.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":14110626,"creator":"khribikova","relation":"source_file","file_id":"6549","checksum":"68949c2d96210b45b981a23e9c9cd93c","date_created":"2019-06-07T13:00:04Z","date_updated":"2020-07-14T12:47:33Z"},{"file_name":"Katarina Valoskova_PhD thesis_final version.pdf","access_level":"open_access","creator":"khribikova","content_type":"application/pdf","file_size":10054156,"file_id":"6550","embargo":"2020-06-07","relation":"main_file","date_created":"2019-06-07T13:00:08Z","date_updated":"2021-02-11T11:17:14Z","checksum":"555329cd76e196c96f5278c480ee2e6e"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6546","title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","ddc":["570"],"status":"public","day":"07","article_processing_charge":"No","has_accepted_license":"1","date_published":"2019-06-07T00:00:00Z","citation":{"apa":"Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546","ieee":"K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019.","ista":"Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria.","ama":"Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546","chicago":"Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546.","short":"K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019.","mla":"Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546."},"page":"141","file_date_updated":"2021-02-11T11:17:14Z","author":[{"last_name":"Valosková","first_name":"Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","full_name":"Valosková, Katarina"}],"related_material":{"record":[{"id":"6187","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"544"}]},"date_created":"2019-06-07T12:49:19Z","date_updated":"2023-09-19T10:15:54Z","year":"2019","publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","month":"06","publication_identifier":{"issn":["2663-337X"]},"doi":"10.15479/AT:ISTA:6546","acknowledged_ssus":[{"_id":"Bio"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353"}],"language":[{"iso":"eng"}],"oa":1,"project":[{"name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283"}]},{"publication_identifier":{"issn":["2663-337X"]},"month":"07","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353"}],"doi":"10.15479/AT:ISTA:th1064","oa":1,"publist_id":"8047","file_date_updated":"2021-02-11T11:17:16Z","date_updated":"2023-09-07T12:43:10Z","date_created":"2018-12-11T11:44:08Z","author":[{"full_name":"Belyaeva, Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87","last_name":"Belyaeva","first_name":"Vera"}],"department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","year":"2018","has_accepted_license":"1","article_processing_charge":"No","day":"01","date_published":"2018-07-01T00:00:00Z","page":"96","citation":{"ama":"Belyaeva V. Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . 2018. doi:10.15479/AT:ISTA:th1064","apa":"Belyaeva, V. (2018). Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1064","ieee":"V. Belyaeva, “Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo ,” Institute of Science and Technology Austria, 2018.","ista":"Belyaeva V. 2018. Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . Institute of Science and Technology Austria.","short":"V. Belyaeva, Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo , Institute of Science and Technology Austria, 2018.","mla":"Belyaeva, Vera. Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1064.","chicago":"Belyaeva, Vera. “Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1064."},"abstract":[{"text":"Immune cells migrating to the sites of infection navigate through diverse tissue architectures and switch their migratory mechanisms upon demand. However, little is known about systemic regulators that could allow the acquisition of these mechanisms. We performed a genetic screen in Drosophila melanogaster to identify regulators of germband invasion by embryonic macrophages into the confined space between the ectoderm and mesoderm. We have found that bZIP circadian transcription factors (TFs) Kayak (dFos) and Vrille (dNFIL3) have opposite effects on macrophage germband infiltration: Kayak facilitated and Vrille inhibited it. These TFs are enriched in the macrophages during migration and genetically interact to control it. Kayak sets a less coordinated mode of migration of the macrophage group and increases the probability and length of Levy walks. Intriguingly, the motility of kayak mutant macrophages was also strongly affected during initial germband invasion but not along another less confined route. Inhibiting Rho1 signaling within the tail ectoderm partially rescued the Kayak mutant phenotype, strongly suggesting that migrating macrophages have to overcome a barrier imposed by the stiffness of the ectoderm. Also, Kayak appeared to be important for the maintenance of the round cell shape and the rear edge translocation of the macrophages invading the germband. Complementary to this, the cortical actin cytoskeleton of Kayak- deficient macrophages was strongly affected. RNA sequencing revealed the filamin Cheerio and tetraspanin TM4SF to be downstream of Kayak. Chromatin immunoprecipitation and immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Indeed, Cheerio, TM4SF and Diaphanous are required within macrophages for germband invasion, and expression of constitutively active Diaphanous in macrophages was able to rescue the kayak mutant phenotype. Moreover, Cher and Diaphanous are also reduced in the macrophages overexpressing Vrille. We hypothesize that Kayak, through its targets, increases actin polymerization and cortical tension in macrophages and thus allows extra force generation necessary for macrophage dissemination and migration through confined stiff tissues, while Vrille counterbalances it.","lang":"eng"}],"alternative_title":["ISTA Thesis"],"type":"dissertation","file":[{"embargo_to":"open_access","file_name":"2018_Thesis_Belyaeva_source.docx","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":102737483,"creator":"dernst","relation":"source_file","file_id":"6243","date_created":"2019-04-08T14:13:12Z","date_updated":"2020-07-14T12:48:14Z","checksum":"d27b2465cb70d0c9678a0381b9b6ced1"},{"checksum":"a2939b61bde2de7b8ced77bbae0eaaed","date_updated":"2021-02-11T11:17:16Z","date_created":"2019-04-08T14:14:08Z","relation":"main_file","file_id":"6244","embargo":"2019-11-19","file_size":88077843,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2018_Thesis_Belyaeva.pdf"}],"oa_version":"Published Version","pubrep_id":"1064","status":"public","ddc":["570"],"title":"Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo ","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"9"}]