{"doi":"10.15479/AT-ISTA-20212","file_date_updated":"2026-08-26T22:30:02Z","OA_place":"publisher","publisher":"Institute of Science and Technology Austria","ddc":["570"],"fulldoi":"https://doi.org/10.15479/AT-ISTA-20212","day":"22","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-063-3"]},"_id":"20212","month":"08","status":"public","year":"2025","alternative_title":["ISTA Thesis"],"title":"Unraveling the role of Pten in cortical stem cell lineage progression using MADM","article_processing_charge":"No","oa":1,"corr_author":"1","keyword":["Pten","mtor","cortical development","MADM","Mapk"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"related_material":{"record":[{"status":"public","id":"17425","relation":"part_of_dissertation"}]},"abstract":[{"lang":"eng","text":"Cortical development has been studied for many decades and with each passing year, we learn \r\nmore about the processes that govern the tightly regulated developmental program. Up until \r\nrecently, the field has struggled to gain reliable access to progenitors at the single-cell level, \r\nlimiting the resolution at which we can study cortical development in vivo. Therefore, much of \r\nthe data we have on mammalian cortical development is at the cell population level. The \r\nsubsequent pages of this thesis describe novel elements of cortical development in mice; \r\nacquired using a candidate gene approach in conjunction with Mosaic Analysis with Double \r\nMarkers (MADM) to achieve single cell resolution. In this thesis, I briefly provide an overview \r\nof the state of the field, describe the methodology used to quantify morphological \r\ncharacteristics of neurons and glia, and delve into the role of Phosphatase and tensin \r\nhomologue on chromosome ten (Pten) in neurogenesis and gliogenesis in the developing mouse \r\ncortex. By using MADM to generate genetic mosaics, in which only a small fraction of cells \r\nare mutated, to study population-level changes, we can bypass the early postnatal lethality \r\nreported in Pten conditional knockouts (cKOs) using Emx1-Cre. We used Emx1-CreERT2 to \r\ninduce clonal deletion of Pten, and quantify RGP neurogenic output at the single progenitor \r\nlevel. Pten-mutant neuron populations within the mosaics were significantly expanded. In the \r\nlatter parts of this thesis, we describe how Pten deletion leads to an increase in the abundance \r\nof astrocytes. We availed ourselves of the flexibility offered by the MADM system to generate \r\nPten mosaics within a series of distinct knockout tissues to test for the interactions between \r\nPten and a battery of genes involved in distinct pro-gliogenic signaling pathways. Our survey \r\nof Pten’s interactions with genes in key signaling pathways reveals that ERK1/2 are the critical \r\neffectors downstream of EGFR signaling essential for gliogenesis. Altogether, our results \r\ndemonstrate that Pten plays critical and distinct roles throughout cortical RGP lineage \r\nprogression. "}],"doi_confirm":"1","author":[{"last_name":"Miranda","first_name":"Osvaldo","orcid":"0000-0001-6618-6889","full_name":"Miranda, Osvaldo","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425"}],"degree_awarded":"PhD","file":[{"embargo_to":"open_access","access_level":"closed","date_created":"2025-08-26T09:03:50Z","creator":"omiranda","file_size":32887334,"file_name":"2025_MirandaRomero_OsvaldoAntonio_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2026-08-26T22:30:02Z","relation":"source_file","checksum":"3331f76bbef74ff4908e2d2c9262045c","file_id":"20230"},{"date_updated":"2026-08-26T22:30:02Z","file_id":"20231","relation":"main_file","checksum":"02509d50cff8e35c5bcbf71e8d658176","content_type":"application/pdf","file_name":"2025_MirandaRomero_OsvaldoAntonio_Thesis.pdf","date_created":"2025-08-26T09:05:55Z","file_size":28636240,"creator":"omiranda","embargo":"2026-08-26","access_level":"open_access"}],"department":[{"_id":"GradSch"},{"_id":"SiHi"}],"publication_status":"published","date_updated":"2026-10-02T12:16:56Z","date_published":"2025-08-22T00:00:00Z","type":"dissertation","has_accepted_license":"1","language":[{"iso":"eng"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_created":"2025-08-22T14:07:00Z","oa_version":"Published Version","page":"119","citation":{"short":"O. Miranda, Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM, Institute of Science and Technology Austria, 2025.","ieee":"O. Miranda, “Unraveling the role of Pten in cortical stem cell lineage progression using MADM,” Institute of Science and Technology Austria, 2025.","mla":"Miranda, Osvaldo. <i>Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20212\">10.15479/AT-ISTA-20212</a>.","apa":"Miranda, O. (2025). <i>Unraveling the role of Pten in cortical stem cell lineage progression using MADM</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20212\">https://doi.org/10.15479/AT-ISTA-20212</a>","ama":"Miranda O. Unraveling the role of Pten in cortical stem cell lineage progression using MADM. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20212\">10.15479/AT-ISTA-20212</a>","ista":"Miranda O. 2025. Unraveling the role of Pten in cortical stem cell lineage progression using MADM. Institute of Science and Technology Austria.","chicago":"Miranda, Osvaldo. “Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20212\">https://doi.org/10.15479/AT-ISTA-20212</a>."},"supervisor":[{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"project":[{"_id":"34c9fbcb-11ca-11ed-8bc3-98fa5658610d","name":"Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression and Astrocyte Development","grant_number":"26253"}],"acknowledgement":"I would also like to\r\nthank the Austrian Academy of Sciences for awarding me a 2-year DOC fellowship\r\n(DOC26253)."}