[{"month":"09","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"oa_version":"Published Version","project":[{"_id":"267AF0E4-B435-11E9-9278-68D0E5697425","name":"The role of morphogens in the regulation of neural tube growth"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"supervisor":[{"first_name":"Anna","last_name":"Kicheva","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87"}],"publication_identifier":{"issn":["2663 - 337X"]},"date_published":"2023-09-13T00:00:00Z","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","status":"public","related_material":{"record":[{"relation":"part_of_dissertation","id":"7883","status":"public"}]},"file":[{"creator":"kkuzmicz","file_id":"14324","relation":"main_file","access_level":"closed","file_name":"PhDThesis_KK_final_pdfA.pdf","content_type":"application/pdf","date_updated":"2023-09-13T10:08:25Z","file_size":10147911,"checksum":"bd83596869c814b24aeff7077d031c0e","embargo_to":"open_access","date_created":"2023-09-13T09:52:52Z","embargo":"2025-03-13"},{"checksum":"aa2757ae4c3478041fd7e62c587d3e4d","file_size":103980668,"date_created":"2023-09-13T09:53:29Z","file_name":"thesis_KK_final_corrections_092023.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2023-09-13T09:53:29Z","access_level":"closed","relation":"source_file","creator":"kkuzmicz","file_id":"14325"}],"alternative_title":["ISTA Thesis"],"title":"Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"AnKi"}],"article_processing_charge":"No","date_created":"2023-09-13T10:07:18Z","author":[{"last_name":"Kuzmicz-Kowalska","first_name":"Katarzyna","full_name":"Kuzmicz-Kowalska, Katarzyna","id":"4CED352A-F248-11E8-B48F-1D18A9856A87"}],"_id":"14323","publisher":"Institute of Science and Technology Austria","file_date_updated":"2023-09-13T10:08:25Z","page":"151","abstract":[{"lang":"eng","text":"Morphogens are signaling molecules that are known for their prominent role in pattern formation within developing tissues. In addition to patterning, morphogens also control tissue growth. However, the underlying mechanisms are poorly understood. We studied the role of morphogens in regulating tissue growth in the developing vertebrate neural tube. In this system, opposing morphogen gradients of Shh and BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations in these morphogen pathways result in alterations in tissue growth and cell cycle progression, however, it has been unclear what cellular process is affected. To address this, we analysed the rates of cell proliferation and cell death in mouse mutants in which signaling is perturbed, as well as in chick neural plate explants exposed to defined concentrations of signaling activators or inhibitors. Our results indicated that the rate of cell proliferation was not altered in these assays. By contrast, both the Shh and BMP signaling pathways had profound effects on neural progenitor survival. Our results indicate that these pathways synergise to promote cell survival within neural progenitors. Consistent with this, we found that progenitors within the intermediate region of the neural tube, where the combined levels of Shh and BMP are the lowest, are most prone to cell death when signaling activity is inhibited. In addition, we found that downregulation of Shh results in increased apoptosis within the roof plate, which is the dorsal source of BMP ligand production. This revealed a cross-interaction between the Shh and BMP morphogen signaling pathways that may be relevant for understanding how gradients scale in neural tubes with different overall sizes. We further studied the mechanism acting downstream of Shh in cell survival regulation using genetic and genomic approaches. We propose that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether, our study points to a novel role of opposing morphogen gradients in tissue size regulation and provides new insights into complex interactions between Shh and BMP signaling gradients in the neural tube."}],"degree_awarded":"PhD","doi":"10.15479/at:ista:14323","day":"13","date_updated":"2024-03-07T15:02:59Z","citation":{"ista":"Kuzmicz-Kowalska K. 2023. Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. Institute of Science and Technology Austria.","mla":"Kuzmicz-Kowalska, Katarzyna. <i>Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/at:ista:14323\">10.15479/at:ista:14323</a>.","short":"K. Kuzmicz-Kowalska, Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord, Institute of Science and Technology Austria, 2023.","ieee":"K. Kuzmicz-Kowalska, “Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord,” Institute of Science and Technology Austria, 2023.","chicago":"Kuzmicz-Kowalska, Katarzyna. “Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/at:ista:14323\">https://doi.org/10.15479/at:ista:14323</a>.","ama":"Kuzmicz-Kowalska K. Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. 2023. doi:<a href=\"https://doi.org/10.15479/at:ista:14323\">10.15479/at:ista:14323</a>","apa":"Kuzmicz-Kowalska, K. (2023). <i>Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:14323\">https://doi.org/10.15479/at:ista:14323</a>"},"year":"2023","ddc":["570"]},{"page":"93","file_date_updated":"2023-05-25T06:32:16Z","publisher":"Institute of Science and Technology Austria","_id":"13081","author":[{"id":"4896F754-F248-11E8-B48F-1D18A9856A87","last_name":"Bocanegra","first_name":"Laura","full_name":"Bocanegra, Laura"}],"article_processing_charge":"No","date_created":"2023-05-23T19:10:42Z","department":[{"_id":"GradSch"},{"_id":"AnKi"}],"publication_status":"published","alternative_title":["ISTA Thesis"],"title":"Epithelial dynamics during mouse neural tube development","ddc":["570"],"citation":{"ista":"Bocanegra L. 2023. Epithelial dynamics during mouse neural tube development. Institute of Science and Technology Austria.","mla":"Bocanegra, Laura. <i>Epithelial Dynamics during Mouse Neural Tube Development</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/at:ista:13081\">10.15479/at:ista:13081</a>.","short":"L. Bocanegra, Epithelial Dynamics during Mouse Neural Tube Development, Institute of Science and Technology Austria, 2023.","ieee":"L. Bocanegra, “Epithelial dynamics during mouse neural tube development,” Institute of Science and Technology Austria, 2023.","chicago":"Bocanegra, Laura. “Epithelial Dynamics during Mouse Neural Tube Development.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/at:ista:13081\">https://doi.org/10.15479/at:ista:13081</a>.","apa":"Bocanegra, L. (2023). <i>Epithelial dynamics during mouse neural tube development</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:13081\">https://doi.org/10.15479/at:ista:13081</a>","ama":"Bocanegra L. Epithelial dynamics during mouse neural tube development. 2023. doi:<a href=\"https://doi.org/10.15479/at:ista:13081\">10.15479/at:ista:13081</a>"},"year":"2023","date_updated":"2023-10-04T11:14:04Z","day":"23","degree_awarded":"PhD","doi":"10.15479/at:ista:13081","abstract":[{"lang":"eng","text":"During development, tissues undergo changes in size and shape to form functional organs. Distinct cellular processes such as cell division and cell rearrangements underlie tissue morphogenesis. Yet how the distinct processes are controlled and coordinated, and how they contribute to morphogenesis is poorly understood. In our study, we addressed these questions using the developing mouse neural tube. This epithelial organ transforms from a flat epithelial sheet to an epithelial tube while increasing in size and undergoing morpho-gen-mediated patterning. The extent and mechanism of neural progenitor rearrangement within the developing mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution lineage tracing analysis to quantify the extent of epithelial rear-rangement at different stages of neural tube development. We quantitatively described the relationship between apical cell size with cell cycle dependent interkinetic nuclear migra-tions (IKNM) and performed high cellular resolution live imaging of the neuroepithelium to study the dynamics of junctional remodeling.  Furthermore, developed a vertex model of the neuroepithelium to investigate the quantitative contribution of cell proliferation, cell differentiation and mechanical properties to the epithelial rearrangement dynamics and validated the model predictions through functional experiments. Our analysis revealed that at early developmental stages, the apical cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in a regime of high junctional tension and contractility. After E9.5, there is a sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium transitions from a fluid-like to a solid-like state. We found that this transition is regulated by the growth rate of the tissue, rather than by changes in cell-cell adhesion and contractile forces. Overall, our study provides a quantitative description of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements and the emergent tissue material properties, and novel insights on how epithelial cell dynamics influences tissue morphogenesis."}],"language":[{"iso":"eng"}],"has_accepted_license":"1","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"month":"05","file":[{"access_level":"closed","relation":"source_file","file_id":"13089","creator":"lbocaneg","date_created":"2023-05-25T06:32:12Z","file_size":25615534,"checksum":"74f3f89e59a0189bee53ebfad9c1b9af","date_updated":"2023-05-25T06:32:12Z","file_name":"Thesis_final_LauraBocanegra.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"},{"relation":"main_file","access_level":"closed","file_id":"13090","creator":"lbocaneg","embargo":"2024-05-31","date_created":"2023-05-25T06:32:16Z","file_size":12386046,"checksum":"c6cdef6323eacfb4b7a8af20f32eae97","embargo_to":"open_access","date_updated":"2023-05-25T06:32:16Z","file_name":"TotalFinal_Thesis_LauraBocanegraArx.pdf","content_type":"application/pdf"}],"status":"public","related_material":{"record":[{"id":"9349","relation":"part_of_dissertation","status":"public"},{"status":"public","id":"12837","relation":"part_of_dissertation"}]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"type":"dissertation","date_published":"2023-05-23T00:00:00Z","publication_identifier":{"issn":["2663 - 337X"]},"supervisor":[{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","first_name":"Anna","last_name":"Kicheva"}]}]