[{"date_updated":"2023-09-22T09:58:30Z","citation":{"ieee":"A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration,” Institute of Science and Technology Austria, 2021.","chicago":"Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>.","ama":"Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>","apa":"Hansen, A. H. (2021). <i>Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>","ista":"Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria.","mla":"Hansen, Andi H. <i>Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>.","short":"A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration, Institute of Science and Technology Austria, 2021."},"year":"2021","degree_awarded":"PhD","doi":"10.15479/at:ista:9962","day":"02","abstract":[{"text":"The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration.","lang":"eng"}],"ddc":["570"],"_id":"9962","license":"https://creativecommons.org/licenses/by/4.0/","author":[{"first_name":"Andi H","last_name":"Hansen","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","date_created":"2021-08-29T12:36:50Z","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"alternative_title":["ISTA Thesis"],"title":"Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration","page":"182","file_date_updated":"2022-09-03T22:30:04Z","publisher":"Institute of Science and Technology Austria","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2021-09-02T00:00:00Z","type":"dissertation","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"oa":1,"file":[{"date_updated":"2022-09-03T22:30:04Z","file_name":"Thesis_Hansen.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2021-08-30T09:17:39Z","checksum":"66b56f5b988b233dc66a4f4b4fb2cdfe","file_size":10629190,"embargo_to":"open_access","file_id":"9971","creator":"ahansen","access_level":"closed","relation":"source_file"},{"file_name":"Thesis_Hansen_PDFA-1a.pdf","content_type":"application/pdf","date_updated":"2022-09-03T22:30:04Z","checksum":"204fa40321a1c6289b68c473634c4bf3","file_size":13457469,"date_created":"2021-08-30T09:29:44Z","embargo":"2022-09-02","creator":"ahansen","file_id":"9972","relation":"main_file","access_level":"open_access"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"8569"},{"relation":"part_of_dissertation","id":"960","status":"public"}]},"has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"month":"09","language":[{"iso":"eng"}],"keyword":["Neuronal migration","Non-cell-autonomous","Cell-autonomous","Neurodevelopmental disease"]},{"language":[{"iso":"eng"}],"month":"06","project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"oa_version":"Published Version","has_accepted_license":"1","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6830"},{"status":"public","id":"28","relation":"dissertation_contains"},{"status":"public","id":"7815","relation":"dissertation_contains"}]},"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2021-06-07T22:30:03Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"PhDThesis_Contreras.docx","date_created":"2020-06-05T08:18:08Z","embargo_to":"open_access","file_size":53134142,"checksum":"43c172bf006c95b65992d473c7240d13","file_id":"7927","creator":"xcontreras","relation":"source_file","access_level":"closed"},{"access_level":"open_access","relation":"main_file","creator":"xcontreras","file_id":"7928","file_size":35117191,"checksum":"addfed9128271be05cae3608e03a6ec0","date_created":"2020-06-05T08:18:07Z","embargo":"2021-06-06","content_type":"application/pdf","file_name":"PhDThesis_Contreras.pdf","date_updated":"2021-06-07T22:30:03Z"}],"oa":1,"supervisor":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon"}],"publication_identifier":{"issn":["2663-337X"]},"type":"dissertation","date_published":"2020-06-05T00:00:00Z","publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-06-07T22:30:03Z","ec_funded":1,"page":"214","alternative_title":["ISTA Thesis"],"title":"Genetic dissection of neural development in health and disease at single cell resolution","article_processing_charge":"No","date_created":"2020-05-29T08:27:32Z","department":[{"_id":"SiHi"}],"publication_status":"published","author":[{"full_name":"Contreras, Ximena","first_name":"Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87"}],"_id":"7902","ddc":["570"],"abstract":[{"text":"Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.","lang":"eng"}],"day":"05","doi":"10.15479/AT:ISTA:7902","degree_awarded":"PhD","citation":{"ista":"Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria.","mla":"Contreras, Ximena. <i>Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>.","short":"X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020.","chicago":"Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>.","ieee":"X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020.","ama":"Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>","apa":"Contreras, X. (2020). <i>Genetic dissection of neural development in health and disease at single cell resolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>"},"year":"2020","date_updated":"2023-10-18T08:45:16Z"}]