[{"author":[{"full_name":"Asaoka, Yoichi","first_name":"Yoichi","last_name":"Asaoka"},{"full_name":"Morita, Hitoshi","first_name":"Hitoshi","last_name":"Morita"},{"first_name":"Hiroko","last_name":"Furumoto","full_name":"Furumoto, Hiroko"},{"full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"},{"last_name":"Furutani-Seiki","first_name":"Makoto","full_name":"Furutani-Seiki, Makoto"}],"oa_version":"None","volume":1893,"date_created":"2019-01-06T22:59:11Z","date_updated":"2021-01-12T08:03:30Z","_id":"5793","year":"2019","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 1893","department":[{"_id":"CaHe"}],"publisher":"Springer","editor":[{"last_name":"Hergovich","first_name":"Alexander","full_name":"Hergovich, Alexander"}],"title":"Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids","status":"public","publication_status":"published","abstract":[{"lang":"eng","text":"The transcription coactivator, Yes-associated protein (YAP), which is a nuclear effector of the Hippo signaling pathway, has been shown to be a mechano-transducer. By using mutant fish and human 3D spheroids, we have recently demonstrated that YAP is also a mechano-effector. YAP functions in three-dimensional (3D) morphogenesis of organ and global body shape by controlling actomyosin-mediated tissue tension. In this chapter, we present a platform that links the findings in fish embryos with human cells. The protocols for analyzing tissue tension-mediated global body shape/organ morphogenesis in vivo and ex vivo using medaka fish embryos and in vitro using human cell spheroids represent useful tools for unraveling the molecular mechanisms by which YAP functions in regulating global body/organ morphogenesis."}],"type":"book_chapter","alternative_title":["MIMB"],"date_published":"2019-01-01T00:00:00Z","doi":"10.1007/978-1-4939-8910-2_14","language":[{"iso":"eng"}],"citation":{"ista":"Asaoka Y, Morita H, Furumoto H, Heisenberg C-PJ, Furutani-Seiki M. 2019.Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids. In: The hippo pathway. MIMB, vol. 1893, 167–181.","apa":"Asaoka, Y., Morita, H., Furumoto, H., Heisenberg, C.-P. J., & Furutani-Seiki, M. (2019). Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids. In A. Hergovich (Ed.), The hippo pathway (Vol. 1893, pp. 167–181). Springer. https://doi.org/10.1007/978-1-4939-8910-2_14","ieee":"Y. Asaoka, H. Morita, H. Furumoto, C.-P. J. Heisenberg, and M. Furutani-Seiki, “Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids,” in The hippo pathway, vol. 1893, A. Hergovich, Ed. Springer, 2019, pp. 167–181.","ama":"Asaoka Y, Morita H, Furumoto H, Heisenberg C-PJ, Furutani-Seiki M. Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids. In: Hergovich A, ed. The Hippo Pathway. Vol 1893. Methods in Molecular Biology. Springer; 2019:167-181. doi:10.1007/978-1-4939-8910-2_14","chicago":"Asaoka, Yoichi, Hitoshi Morita, Hiroko Furumoto, Carl-Philipp J Heisenberg, and Makoto Furutani-Seiki. “Studying YAP-Mediated 3D Morphogenesis Using Fish Embryos and Human Spheroids.” In The Hippo Pathway, edited by Alexander Hergovich, 1893:167–81. Methods in Molecular Biology. Springer, 2019. https://doi.org/10.1007/978-1-4939-8910-2_14.","mla":"Asaoka, Yoichi, et al. “Studying YAP-Mediated 3D Morphogenesis Using Fish Embryos and Human Spheroids.” The Hippo Pathway, edited by Alexander Hergovich, vol. 1893, Springer, 2019, pp. 167–81, doi:10.1007/978-1-4939-8910-2_14.","short":"Y. Asaoka, H. Morita, H. Furumoto, C.-P.J. Heisenberg, M. Furutani-Seiki, in:, A. Hergovich (Ed.), The Hippo Pathway, Springer, 2019, pp. 167–181."},"publication":"The hippo pathway","page":"167-181","quality_controlled":"1","publication_identifier":{"isbn":["978-1-4939-8909-6"]},"day":"01","month":"01","scopus_import":1,"series_title":"Methods in Molecular Biology"},{"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaHe"},{"_id":"HaJa"}],"year":"2019","date_created":"2019-02-17T22:59:22Z","date_updated":"2023-08-24T14:46:01Z","volume":8,"author":[{"orcid":"0000-0001-5199-9940","id":"31C42484-F248-11E8-B48F-1D18A9856A87","last_name":"Capek","first_name":"Daniel","full_name":"Capek, Daniel"},{"full_name":"Smutny, Michael","first_name":"Michael","last_name":"Smutny","id":"3FE6E4E8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5920-9090"},{"last_name":"Tichy","first_name":"Alexandra Madelaine","full_name":"Tichy, Alexandra Madelaine"},{"full_name":"Morri, Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87","first_name":"Maurizio","last_name":"Morri"},{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"article_number":"e42093","file_date_updated":"2020-07-14T12:47:17Z","ec_funded":1,"quality_controlled":"1","isi":1,"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"}],"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"},"external_id":{"isi":["000458025300001"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.7554/eLife.42093","month":"02","status":"public","title":"Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration","ddc":["570"],"intvolume":" 8","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6025","oa_version":"Published Version","file":[{"creator":"dernst","content_type":"application/pdf","file_size":5500707,"file_name":"2019_elife_Capek.pdf","access_level":"open_access","date_updated":"2020-07-14T12:47:17Z","date_created":"2019-02-18T15:17:21Z","checksum":"6cb4ca6d4aa96f6f187a5983aa3e660a","file_id":"6041","relation":"main_file"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation."}],"publication":"eLife","citation":{"short":"D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg, ELife 8 (2019).","mla":"Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife, vol. 8, e42093, eLife Sciences Publications, 2019, doi:10.7554/eLife.42093.","chicago":"Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri, Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42093.","ama":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 2019;8. doi:10.7554/eLife.42093","apa":"Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., & Heisenberg, C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42093","ieee":"D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg, “Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration,” eLife, vol. 8. eLife Sciences Publications, 2019.","ista":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 8, e42093."},"date_published":"2019-02-06T00:00:00Z","scopus_import":"1","day":"06","has_accepted_license":"1","article_processing_charge":"No"},{"date_published":"2019-03-07T00:00:00Z","publication":"Cell","citation":{"chicago":"Xia, Peng, Daniel J Gütl, Vanessa Zheden, and Carl-Philipp J Heisenberg. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.01.019.","mla":"Xia, Peng, et al. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” Cell, vol. 176, no. 6, Elsevier, 2019, p. 1379–1392.e14, doi:10.1016/j.cell.2019.01.019.","short":"P. Xia, D.J. Gütl, V. Zheden, C.-P.J. Heisenberg, Cell 176 (2019) 1379–1392.e14.","ista":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. 2019. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 176(6), 1379–1392.e14.","apa":"Xia, P., Gütl, D. J., Zheden, V., & Heisenberg, C.-P. J. (2019). Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.01.019","ieee":"P. Xia, D. J. Gütl, V. Zheden, and C.-P. J. Heisenberg, “Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity,” Cell, vol. 176, no. 6. Elsevier, p. 1379–1392.e14, 2019.","ama":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 2019;176(6):1379-1392.e14. doi:10.1016/j.cell.2019.01.019"},"article_type":"original","page":"1379-1392.e14","day":"07","article_processing_charge":"No","scopus_import":"1","oa_version":"Published Version","_id":"6087","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity","status":"public","intvolume":" 176","abstract":[{"text":"Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.","lang":"eng"}],"issue":"6","type":"journal_article","doi":"10.1016/j.cell.2019.01.019","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"external_id":{"pmid":["30773315"],"isi":["000460509600013"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.01.019"}],"quality_controlled":"1","isi":1,"project":[{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"month":"03","author":[{"full_name":"Xia, Peng","first_name":"Peng","last_name":"Xia","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5419-7756"},{"first_name":"Daniel J","last_name":"Gütl","id":"381929CE-F248-11E8-B48F-1D18A9856A87","full_name":"Gütl, Daniel J"},{"first_name":"Vanessa","last_name":"Zheden","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9438-4783","full_name":"Zheden, Vanessa"},{"full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/in-zebrafish-eggs-most-rapidly-growing-cell-inhibits-its-neighbours-through-mechanical-signals/","description":"News on IST Homepage","relation":"press_release"}]},"date_created":"2019-03-10T22:59:19Z","date_updated":"2023-08-25T08:02:23Z","volume":176,"year":"2019","acknowledgement":"We thank Roland Dosch, Makoto Furutani-Seiki, Brian Link, Mary Mullins, and Masazumi Tada for providing transgenic and/or mutant zebrafish lines; Alexandra Schauer, Shayan Shami-Pour, and the rest of the Heisenberg lab for technical assistance and feedback on the manuscript; and the Bioimaging, Electron Microscopy, and Zebrafish facilities of IST Austria for continuous support. This work was supported by an ERC advanced grant ( MECSPEC to C.-P.H.).","pmid":1,"publication_status":"published","department":[{"_id":"CaHe"},{"_id":"EM-Fac"}],"publisher":"Elsevier","ec_funded":1},{"page":"12-25","article_type":"review","citation":{"ama":"Hannezo EB, Heisenberg C-PJ. Mechanochemical feedback loops in development and disease. Cell. 2019;178(1):12-25. doi:10.1016/j.cell.2019.05.052","ista":"Hannezo EB, Heisenberg C-PJ. 2019. Mechanochemical feedback loops in development and disease. Cell. 178(1), 12–25.","ieee":"E. B. Hannezo and C.-P. J. Heisenberg, “Mechanochemical feedback loops in development and disease,” Cell, vol. 178, no. 1. Elsevier, pp. 12–25, 2019.","apa":"Hannezo, E. B., & Heisenberg, C.-P. J. (2019). Mechanochemical feedback loops in development and disease. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.05.052","mla":"Hannezo, Edouard B., and Carl-Philipp J. Heisenberg. “Mechanochemical Feedback Loops in Development and Disease.” Cell, vol. 178, no. 1, Elsevier, 2019, pp. 12–25, doi:10.1016/j.cell.2019.05.052.","short":"E.B. Hannezo, C.-P.J. Heisenberg, Cell 178 (2019) 12–25.","chicago":"Hannezo, Edouard B, and Carl-Philipp J Heisenberg. “Mechanochemical Feedback Loops in Development and Disease.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.05.052."},"publication":"Cell","date_published":"2019-07-27T00:00:00Z","scopus_import":"1","article_processing_charge":"No","day":"27","intvolume":" 178","title":"Mechanochemical feedback loops in development and disease","status":"public","_id":"6601","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","type":"journal_article","issue":"1","abstract":[{"text":"There is increasing evidence that both mechanical and biochemical signals play important roles in development and disease. The development of complex organisms, in particular, has been proposed to rely on the feedback between mechanical and biochemical patterning events. This feedback occurs at the molecular level via mechanosensation but can also arise as an emergent property of the system at the cellular and tissue level. In recent years, dynamic changes in tissue geometry, flow, rheology, and cell fate specification have emerged as key platforms of mechanochemical feedback loops in multiple processes. Here, we review recent experimental and theoretical advances in understanding how these feedbacks function in development and disease.","lang":"eng"}],"project":[{"call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"},{"name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF","grant_number":"P31639","_id":"268294B6-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000473002700005"],"pmid":["31251912"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.05.052"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2019.05.052","publication_identifier":{"issn":["00928674"]},"month":"07","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"year":"2019","volume":178,"date_created":"2019-06-30T21:59:11Z","date_updated":"2023-08-28T12:25:21Z","author":[{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"ec_funded":1},{"publication_identifier":{"issn":["0955-0674"]},"article_processing_charge":"No","day":"01","month":"10","scopus_import":"1","language":[{"iso":"eng"}],"doi":"10.1016/j.ceb.2019.05.007","date_published":"2019-10-01T00:00:00Z","page":"114-120","quality_controlled":"1","isi":1,"citation":{"short":"B.G. Godard, C.-P.J. Heisenberg, Current Opinion in Cell Biology 60 (2019) 114–120.","mla":"Godard, Benoit G., and Carl-Philipp J. Heisenberg. “Cell Division and Tissue Mechanics.” Current Opinion in Cell Biology, vol. 60, Elsevier, 2019, pp. 114–20, doi:10.1016/j.ceb.2019.05.007.","chicago":"Godard, Benoit G, and Carl-Philipp J Heisenberg. “Cell Division and Tissue Mechanics.” Current Opinion in Cell Biology. Elsevier, 2019. https://doi.org/10.1016/j.ceb.2019.05.007.","ama":"Godard BG, Heisenberg C-PJ. Cell division and tissue mechanics. Current Opinion in Cell Biology. 2019;60:114-120. doi:10.1016/j.ceb.2019.05.007","apa":"Godard, B. G., & Heisenberg, C.-P. J. (2019). Cell division and tissue mechanics. Current Opinion in Cell Biology. Elsevier. https://doi.org/10.1016/j.ceb.2019.05.007","ieee":"B. G. Godard and C.-P. J. Heisenberg, “Cell division and tissue mechanics,” Current Opinion in Cell Biology, vol. 60. Elsevier, pp. 114–120, 2019.","ista":"Godard BG, Heisenberg C-PJ. 2019. Cell division and tissue mechanics. Current Opinion in Cell Biology. 60, 114–120."},"external_id":{"isi":["000486545800016"]},"publication":"Current Opinion in Cell Biology","abstract":[{"lang":"eng","text":"The spatiotemporal organization of cell divisions constitutes an integral part in the development of multicellular organisms, and mis-regulation of cell divisions can lead to severe developmental defects. Cell divisions have an important morphogenetic function in development by regulating growth and shape acquisition of developing tissues, and, conversely, tissue morphogenesis is known to affect both the rate and orientation of cell divisions. Moreover, cell divisions are associated with an extensive reorganization of the cytoskeleton and adhesion apparatus in the dividing cells that in turn can affect large-scale tissue rheological properties. Thus, the interplay between cell divisions and tissue morphogenesis plays a key role in embryo and tissue morphogenesis."}],"type":"journal_article","oa_version":"None","volume":60,"date_created":"2019-07-14T21:59:17Z","date_updated":"2023-08-29T06:33:14Z","author":[{"full_name":"Godard, Benoit G","id":"33280250-F248-11E8-B48F-1D18A9856A87","first_name":"Benoit G","last_name":"Godard"},{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"intvolume":" 60","publisher":"Elsevier","department":[{"_id":"CaHe"}],"title":"Cell division and tissue mechanics","publication_status":"published","status":"public","_id":"6631","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","year":"2019"},{"author":[{"orcid":"0000-0001-9970-7804","id":"2F162F0C-F248-11E8-B48F-1D18A9856A87","last_name":"Tavano","first_name":"Ste","full_name":"Tavano, Ste"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"volume":21,"date_updated":"2023-08-29T07:42:20Z","date_created":"2019-09-01T22:00:57Z","pmid":1,"year":"2019","department":[{"_id":"CaHe"}],"publisher":"Springer Nature","publication_status":"published","publication_identifier":{"eissn":["1476-4679"]},"month":"08","doi":"10.1038/s41556-019-0369-3","language":[{"iso":"eng"}],"external_id":{"pmid":["31371826"],"isi":["000478029000003"]},"quality_controlled":"1","isi":1,"issue":"8","abstract":[{"text":"Migrasomes are a recently discovered type of extracellular vesicles that are characteristically generated along retraction fibers in migrating cells. Two studies now show how migrasomes are formed and how they function in the physiologically relevant context of the developing zebrafish embryo.","lang":"eng"}],"type":"journal_article","oa_version":"None","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6837","intvolume":" 21","title":"Migrasomes take center stage","status":"public","article_processing_charge":"No","day":"01","scopus_import":"1","date_published":"2019-08-01T00:00:00Z","citation":{"apa":"Tavano, S., & Heisenberg, C.-P. J. (2019). Migrasomes take center stage. Nature Cell Biology. Springer Nature. https://doi.org/10.1038/s41556-019-0369-3","ieee":"S. Tavano and C.-P. J. Heisenberg, “Migrasomes take center stage,” Nature Cell Biology, vol. 21, no. 8. Springer Nature, pp. 918–920, 2019.","ista":"Tavano S, Heisenberg C-PJ. 2019. Migrasomes take center stage. Nature Cell Biology. 21(8), 918–920.","ama":"Tavano S, Heisenberg C-PJ. Migrasomes take center stage. Nature Cell Biology. 2019;21(8):918-920. doi:10.1038/s41556-019-0369-3","chicago":"Tavano, Ste, and Carl-Philipp J Heisenberg. “Migrasomes Take Center Stage.” Nature Cell Biology. Springer Nature, 2019. https://doi.org/10.1038/s41556-019-0369-3.","short":"S. Tavano, C.-P.J. Heisenberg, Nature Cell Biology 21 (2019) 918–920.","mla":"Tavano, Ste, and Carl-Philipp J. Heisenberg. “Migrasomes Take Center Stage.” Nature Cell Biology, vol. 21, no. 8, Springer Nature, 2019, pp. 918–20, doi:10.1038/s41556-019-0369-3."},"publication":"Nature Cell Biology","page":"918-920"},{"isi":1,"quality_controlled":"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"},"oa":1,"external_id":{"isi":["000485216800009"],"pmid":["31511517"]},"language":[{"iso":"eng"}],"doi":"10.1038/s41467-019-12068-x","month":"09","publication_identifier":{"eissn":["20411723"]},"publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"CaHe"}],"year":"2019","pmid":1,"date_updated":"2023-08-30T06:21:23Z","date_created":"2019-09-22T22:00:37Z","volume":10,"author":[{"full_name":"Bornhorst, Dorothee","last_name":"Bornhorst","first_name":"Dorothee"},{"full_name":"Xia, Peng","orcid":"0000-0002-5419-7756","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","last_name":"Xia","first_name":"Peng"},{"full_name":"Nakajima, Hiroyuki","last_name":"Nakajima","first_name":"Hiroyuki"},{"full_name":"Dingare, Chaitanya","last_name":"Dingare","first_name":"Chaitanya"},{"first_name":"Wiebke","last_name":"Herzog","full_name":"Herzog, Wiebke"},{"full_name":"Lecaudey, Virginie","first_name":"Virginie","last_name":"Lecaudey"},{"full_name":"Mochizuki, Naoki","last_name":"Mochizuki","first_name":"Naoki"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"},{"full_name":"Yelon, Deborah","first_name":"Deborah","last_name":"Yelon"},{"full_name":"Abdelilah-Seyfried, Salim","last_name":"Abdelilah-Seyfried","first_name":"Salim"}],"file_date_updated":"2020-07-14T12:47:44Z","page":"4113","publication":"Nature communications","citation":{"ista":"Bornhorst D, Xia P, Nakajima H, Dingare C, Herzog W, Lecaudey V, Mochizuki N, Heisenberg C-PJ, Yelon D, Abdelilah-Seyfried S. 2019. Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions. Nature communications. 10(1), 4113.","ieee":"D. Bornhorst et al., “Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions,” Nature communications, vol. 10, no. 1. Nature Publishing Group, p. 4113, 2019.","apa":"Bornhorst, D., Xia, P., Nakajima, H., Dingare, C., Herzog, W., Lecaudey, V., … Abdelilah-Seyfried, S. (2019). Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-019-12068-x","ama":"Bornhorst D, Xia P, Nakajima H, et al. Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions. Nature communications. 2019;10(1):4113. doi:10.1038/s41467-019-12068-x","chicago":"Bornhorst, Dorothee, Peng Xia, Hiroyuki Nakajima, Chaitanya Dingare, Wiebke Herzog, Virginie Lecaudey, Naoki Mochizuki, Carl-Philipp J Heisenberg, Deborah Yelon, and Salim Abdelilah-Seyfried. “Biomechanical Signaling within the Developing Zebrafish Heart Attunes Endocardial Growth to Myocardial Chamber Dimensions.” Nature Communications. Nature Publishing Group, 2019. https://doi.org/10.1038/s41467-019-12068-x.","mla":"Bornhorst, Dorothee, et al. “Biomechanical Signaling within the Developing Zebrafish Heart Attunes Endocardial Growth to Myocardial Chamber Dimensions.” Nature Communications, vol. 10, no. 1, Nature Publishing Group, 2019, p. 4113, doi:10.1038/s41467-019-12068-x.","short":"D. Bornhorst, P. Xia, H. Nakajima, C. Dingare, W. Herzog, V. Lecaudey, N. Mochizuki, C.-P.J. Heisenberg, D. Yelon, S. Abdelilah-Seyfried, Nature Communications 10 (2019) 4113."},"date_published":"2019-09-11T00:00:00Z","scopus_import":"1","day":"11","has_accepted_license":"1","article_processing_charge":"No","title":"Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions","status":"public","ddc":["570"],"intvolume":" 10","_id":"6899","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_id":"6926","relation":"main_file","checksum":"62c2512712e16d27c1797d318d14ba9f","date_updated":"2020-07-14T12:47:44Z","date_created":"2019-10-01T11:18:50Z","access_level":"open_access","file_name":"2019_Nature_Bornhorst.pdf","creator":"kschuh","file_size":3905793,"content_type":"application/pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Intra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed.","lang":"eng"}],"issue":"1"},{"month":"10","publication_identifier":{"issn":["0261-4189"],"eissn":["1460-2075"]},"quality_controlled":"1","isi":1,"project":[{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"},{"name":"Tissue material properties in embryonic development","call_identifier":"FWF","grant_number":"V00736","_id":"2693FD8C-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000485561900001"],"pmid":["31512749"]},"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"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.15252/embj.2019102497","article_number":"e102497","file_date_updated":"2020-07-14T12:47:46Z","ec_funded":1,"publication_status":"published","publisher":"EMBO","department":[{"_id":"CaHe"}],"year":"2019","pmid":1,"date_updated":"2023-09-05T13:04:13Z","date_created":"2019-11-04T15:24:29Z","volume":38,"author":[{"full_name":"Petridou, Nicoletta","first_name":"Nicoletta","last_name":"Petridou","id":"2A003F6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8451-1195"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"scopus_import":"1","day":"15","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","article_type":"review","publication":"The EMBO Journal","citation":{"ama":"Petridou N, Heisenberg C-PJ. Tissue rheology in embryonic organization. The EMBO Journal. 2019;38(20). doi:10.15252/embj.2019102497","ieee":"N. Petridou and C.-P. J. Heisenberg, “Tissue rheology in embryonic organization,” The EMBO Journal, vol. 38, no. 20. EMBO, 2019.","apa":"Petridou, N., & Heisenberg, C.-P. J. (2019). Tissue rheology in embryonic organization. The EMBO Journal. EMBO. https://doi.org/10.15252/embj.2019102497","ista":"Petridou N, Heisenberg C-PJ. 2019. Tissue rheology in embryonic organization. The EMBO Journal. 38(20), e102497.","short":"N. Petridou, C.-P.J. Heisenberg, The EMBO Journal 38 (2019).","mla":"Petridou, Nicoletta, and Carl-Philipp J. Heisenberg. “Tissue Rheology in Embryonic Organization.” The EMBO Journal, vol. 38, no. 20, e102497, EMBO, 2019, doi:10.15252/embj.2019102497.","chicago":"Petridou, Nicoletta, and Carl-Philipp J Heisenberg. “Tissue Rheology in Embryonic Organization.” The EMBO Journal. EMBO, 2019. https://doi.org/10.15252/embj.2019102497."},"date_published":"2019-10-15T00:00:00Z","type":"journal_article","abstract":[{"text":"Tissue morphogenesis in multicellular organisms is brought about by spatiotemporal coordination of mechanical and chemical signals. Extensive work on how mechanical forces together with the well‐established morphogen signalling pathways can actively shape living tissues has revealed evolutionary conserved mechanochemical features of embryonic development. More recently, attention has been drawn to the description of tissue material properties and how they can influence certain morphogenetic processes. Interestingly, besides the role of tissue material properties in determining how much tissues deform in response to force application, there is increasing theoretical and experimental evidence, suggesting that tissue material properties can abruptly and drastically change in development. These changes resemble phase transitions, pointing at the intriguing possibility that important morphogenetic processes in development, such as symmetry breaking and self‐organization, might be mediated by tissue phase transitions. In this review, we summarize recent findings on the regulation and role of tissue material properties in the context of the developing embryo. We posit that abrupt changes of tissue rheological properties may have important implications in maintaining the balance between robustness and adaptability during embryonic development.","lang":"eng"}],"issue":"20","status":"public","title":"Tissue rheology in embryonic organization","ddc":["570"],"intvolume":" 38","_id":"6980","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"checksum":"76f7f4e79ab6d850c30017a69726fd85","date_created":"2019-11-04T15:30:08Z","date_updated":"2020-07-14T12:47:46Z","file_id":"6981","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":847356,"access_level":"open_access","file_name":"2019_Embo_Petridou.pdf"}]},{"doi":"10.1007/978-3-030-23459-1_6","language":[{"iso":"eng"}],"oa":1,"external_id":{"pmid":["31598855"]},"quality_controlled":"1","publication_identifier":{"issn":["0080-1844"],"isbn":["9783030234584","9783030234591"],"eissn":["1861-0412"]},"month":"10","author":[{"last_name":"McDougall","first_name":"Alex","full_name":"McDougall, Alex"},{"full_name":"Chenevert, Janet","last_name":"Chenevert","first_name":"Janet"},{"id":"33280250-F248-11E8-B48F-1D18A9856A87","first_name":"Benoit G","last_name":"Godard","full_name":"Godard, Benoit G"},{"full_name":"Dumollard, Remi","first_name":"Remi","last_name":"Dumollard"}],"volume":68,"date_updated":"2023-09-05T15:01:12Z","date_created":"2019-11-04T16:20:19Z","pmid":1,"year":"2019","department":[{"_id":"CaHe"}],"editor":[{"first_name":"Waclaw","last_name":"Tworzydlo","full_name":"Tworzydlo, Waclaw"},{"full_name":"Bilinski, Szczepan M.","first_name":"Szczepan M.","last_name":"Bilinski"}],"publisher":"Springer Nature","publication_status":"published","file_date_updated":"2020-07-14T12:47:46Z","date_published":"2019-10-10T00:00:00Z","citation":{"ieee":"A. McDougall, J. Chenevert, B. G. Godard, and R. Dumollard, “Emergence of embryo shape during cleavage divisions,” in Evo-Devo: Non-model species in cell and developmental biology, vol. 68, W. Tworzydlo and S. M. Bilinski, Eds. Springer Nature, 2019, pp. 127–154.","apa":"McDougall, A., Chenevert, J., Godard, B. G., & Dumollard, R. (2019). Emergence of embryo shape during cleavage divisions. In W. Tworzydlo & S. M. Bilinski (Eds.), Evo-Devo: Non-model species in cell and developmental biology (Vol. 68, pp. 127–154). Springer Nature. https://doi.org/10.1007/978-3-030-23459-1_6","ista":"McDougall A, Chenevert J, Godard BG, Dumollard R. 2019.Emergence of embryo shape during cleavage divisions. In: Evo-Devo: Non-model species in cell and developmental biology. RESULTS, vol. 68, 127–154.","ama":"McDougall A, Chenevert J, Godard BG, Dumollard R. Emergence of embryo shape during cleavage divisions. In: Tworzydlo W, Bilinski SM, eds. Evo-Devo: Non-Model Species in Cell and Developmental Biology. Vol 68. Springer Nature; 2019:127-154. doi:10.1007/978-3-030-23459-1_6","chicago":"McDougall, Alex, Janet Chenevert, Benoit G Godard, and Remi Dumollard. “Emergence of Embryo Shape during Cleavage Divisions.” In Evo-Devo: Non-Model Species in Cell and Developmental Biology, edited by Waclaw Tworzydlo and Szczepan M. Bilinski, 68:127–54. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-23459-1_6.","short":"A. McDougall, J. Chenevert, B.G. Godard, R. Dumollard, in:, W. Tworzydlo, S.M. Bilinski (Eds.), Evo-Devo: Non-Model Species in Cell and Developmental Biology, Springer Nature, 2019, pp. 127–154.","mla":"McDougall, Alex, et al. “Emergence of Embryo Shape during Cleavage Divisions.” Evo-Devo: Non-Model Species in Cell and Developmental Biology, edited by Waclaw Tworzydlo and Szczepan M. Bilinski, vol. 68, Springer Nature, 2019, pp. 127–54, doi:10.1007/978-3-030-23459-1_6."},"publication":"Evo-Devo: Non-model species in cell and developmental biology","page":"127-154","article_processing_charge":"No","has_accepted_license":"1","day":"10","scopus_import":"1","oa_version":"Submitted Version","file":[{"access_level":"open_access","file_name":"2019_RESULTS_McDougall.pdf","file_size":19317348,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"7829","checksum":"7f43e1e3706d15061475c5c57efc2786","date_created":"2020-05-14T10:09:30Z","date_updated":"2020-07-14T12:47:46Z"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6987","intvolume":" 68","title":"Emergence of embryo shape during cleavage divisions","status":"public","ddc":["570"],"abstract":[{"text":"Cells are arranged into species-specific patterns during early embryogenesis. Such cell division patterns are important since they often reflect the distribution of localized cortical factors from eggs/fertilized eggs to specific cells as well as the emergence of organismal form. However, it has proven difficult to reveal the mechanisms that underlie the emergence of cell positioning patterns that underlie embryonic shape, likely because a systems-level approach is required that integrates cell biological, genetic, developmental, and mechanical parameters. The choice of organism to address such questions is also important. Because ascidians display the most extreme form of invariant cleavage pattern among the metazoans, we have been analyzing the cell biological mechanisms that underpin three aspects of cell division (unequal cell division (UCD), oriented cell division (OCD), and asynchronous cell cycles) which affect the overall shape of the blastula-stage ascidian embryo composed of 64 cells. In ascidians, UCD creates two small cells at the 16-cell stage that in turn undergo two further successive rounds of UCD. Starting at the 16-cell stage, the cell cycle becomes asynchronous, whereby the vegetal half divides before the animal half, thus creating 24-, 32-, 44-, and then 64-cell stages. Perturbing either UCD or the alternate cell division rhythm perturbs cell position. We propose that dynamic cell shape changes propagate throughout the embryo via cell-cell contacts to create the ascidian-specific invariant cleavage pattern.","lang":"eng"}],"type":"book_chapter","alternative_title":["RESULTS"]},{"month":"12","publication_identifier":{"issn":["2663-337X"]},"oa":1,"doi":"10.15479/AT:ISTA:7186","supervisor":[{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"}],"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"SSU"}],"language":[{"iso":"eng"}],"file_date_updated":"2020-07-14T12:47:52Z","year":"2019","publication_status":"published","department":[{"_id":"CaHe"}],"publisher":"Institute of Science and Technology Austria","author":[{"last_name":"Schwayer","first_name":"Cornelia","orcid":"0000-0001-5130-2226","id":"3436488C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwayer, Cornelia"}],"related_material":{"record":[{"id":"1096","relation":"dissertation_contains","status":"public"},{"id":"7001","status":"public","relation":"part_of_dissertation"}]},"date_updated":"2023-09-07T12:56:42Z","date_created":"2019-12-16T14:26:14Z","day":"16","article_processing_charge":"No","has_accepted_license":"1","citation":{"ista":"Schwayer C. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria.","ieee":"C. Schwayer, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” Institute of Science and Technology Austria, 2019.","apa":"Schwayer, C. (2019). Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7186","ama":"Schwayer C. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. 2019. doi:10.15479/AT:ISTA:7186","chicago":"Schwayer, Cornelia. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7186.","mla":"Schwayer, Cornelia. Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7186.","short":"C. Schwayer, Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow, Institute of Science and Technology Austria, 2019."},"page":"107","date_published":"2019-12-16T00:00:00Z","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"Tissue morphogenesis in developmental or physiological processes is regulated by molecular\r\nand mechanical signals. While the molecular signaling cascades are increasingly well\r\ndescribed, the mechanical signals affecting tissue shape changes have only recently been\r\nstudied in greater detail. To gain more insight into the mechanochemical and biophysical\r\nbasis of an epithelial spreading process (epiboly) in early zebrafish development, we studied\r\ncell-cell junction formation and actomyosin network dynamics at the boundary between\r\nsurface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,\r\nthe cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of\r\ngastrulation. It has been previously shown that an actomyosin ring residing within the YSL\r\npulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby\r\ndragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL\r\nactomyosin ring to EVL cells; however, the nature and formation of the junctional structure\r\nmediating this process has not been well described so far. Therefore, our main aim was to\r\ndetermine the nature, dynamics and potential function of the EVL-YSL junction during this\r\nepithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a\r\nmechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process\r\nof TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated\r\nZonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we\r\ncould demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk\r\ncell, and ZO-1 undergoes a phase separation process that likely renders the protein\r\nresponsive to flows. These flows are directed towards the junction and mediate proper\r\ntension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets\r\nincorporated into the junctional pool mediated through its direct actin-binding domain.\r\nWhen the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their\r\nproper mechanosensitive responses resulting in slower tissue spreading. We could further\r\ndemonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin\r\nring formation. This suggests that a mechanochemical feedback loop is at work during\r\nzebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin\r\ncontractility and flows positively influence ZO-1 junctional recruitment. Finally, such a\r\nmesoscale polarization process mediated through the flow of phase-separated protein\r\nclusters might have implications for other processes such as immunological synapse\r\nformation, C. elegans zygote polarization and wound healing.","lang":"eng"}],"_id":"7186","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","ddc":["570"],"title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","oa_version":"Published Version","file":[{"file_id":"7194","relation":"source_file","date_updated":"2020-07-14T12:47:52Z","date_created":"2019-12-19T15:18:11Z","checksum":"585583c1c875c5d9525703a539668a7c","file_name":"DocumentSourceFiles.zip","access_level":"closed","creator":"cschwayer","file_size":19431292,"content_type":"application/zip"},{"file_id":"7195","relation":"main_file","checksum":"9b9b24351514948d27cec659e632e2cd","date_created":"2019-12-19T15:19:21Z","date_updated":"2020-07-14T12:47:52Z","access_level":"open_access","file_name":"Thesis_CS_final.pdf","creator":"cschwayer","content_type":"application/pdf","file_size":19226428}]}]