[{"day":"13","year":"2023","has_accepted_license":"1","date_created":"2023-09-13T10:07:18Z","date_published":"2023-09-13T00:00:00Z","doi":"10.15479/at:ista:14323","page":"151","publisher":"Institute of Science and Technology Austria","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"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. https://doi.org/10.15479/at:ista:14323.","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. Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14323.","apa":"Kuzmicz-Kowalska, K. (2023). Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14323","ama":"Kuzmicz-Kowalska K. Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. 2023. doi:10.15479/at:ista:14323","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."},"title":"Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord","article_processing_charge":"No","author":[{"last_name":"Kuzmicz-Kowalska","full_name":"Kuzmicz-Kowalska, Katarzyna","id":"4CED352A-F248-11E8-B48F-1D18A9856A87","first_name":"Katarzyna"}],"project":[{"_id":"267AF0E4-B435-11E9-9278-68D0E5697425","name":"The role of morphogens in the regulation of neural tube growth"}],"language":[{"iso":"eng"}],"file":[{"creator":"kkuzmicz","date_updated":"2023-09-13T10:08:25Z","file_size":10147911,"date_created":"2023-09-13T09:52:52Z","file_name":"PhDThesis_KK_final_pdfA.pdf","access_level":"closed","relation":"main_file","content_type":"application/pdf","embargo_to":"open_access","file_id":"14324","checksum":"bd83596869c814b24aeff7077d031c0e","embargo":"2025-03-13"},{"file_name":"thesis_KK_final_corrections_092023.docx","date_created":"2023-09-13T09:53:29Z","file_size":103980668,"date_updated":"2023-09-13T09:53:29Z","creator":"kkuzmicz","file_id":"14325","checksum":"aa2757ae4c3478041fd7e62c587d3e4d","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663 - 337X"]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","related_material":{"record":[{"relation":"part_of_dissertation","id":"7883","status":"public"}]},"oa_version":"Published Version","abstract":[{"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.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"month":"09","alternative_title":["ISTA Thesis"],"ddc":["570"],"date_updated":"2024-03-07T15:02:59Z","supervisor":[{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","first_name":"Anna","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","last_name":"Kicheva"}],"department":[{"_id":"GradSch"},{"_id":"AnKi"}],"file_date_updated":"2023-09-13T10:08:25Z","_id":"14323","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"dissertation"},{"oa":1,"publisher":"Wiley","quality_controlled":"1","acknowledgement":"Austrian Academy of Sciences, Grant/Award Number: DOC fellowship for Katarzyna Kuzmicz-Kowalska; Austrian Science Fund, Grant/Award Number: F78 (Stem Cell Modulation); H2020 European Research Council, Grant/Award Number: 680037","date_created":"2020-05-24T22:01:00Z","date_published":"2021-04-15T00:00:00Z","doi":"10.1002/wdev.383","publication":"Wiley Interdisciplinary Reviews: Developmental Biology","day":"15","year":"2021","isi":1,"has_accepted_license":"1","project":[{"grant_number":"680037","name":"Coordination of Patterning And Growth In the Spinal Cord","_id":"B6FC0238-B512-11E9-945C-1524E6697425","call_identifier":"H2020"},{"_id":"267AF0E4-B435-11E9-9278-68D0E5697425","name":"The role of morphogens in the regulation of neural tube growth"},{"_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Morphogen control of growth and pattern in the spinal cord","grant_number":"F07802"}],"article_number":"e383","title":"Regulation of size and scale in vertebrate spinal cord development","external_id":{"isi":["000531419400001"],"pmid":["32391980"]},"article_processing_charge":"Yes (via OA deal)","author":[{"id":"4CED352A-F248-11E8-B48F-1D18A9856A87","first_name":"Katarzyna","full_name":"Kuzmicz-Kowalska, Katarzyna","last_name":"Kuzmicz-Kowalska"},{"last_name":"Kicheva","full_name":"Kicheva, Anna","orcid":"0000-0003-4509-4998","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","first_name":"Anna"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Kuzmicz-Kowalska K, Kicheva A. 2021. Regulation of size and scale in vertebrate spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology., e383.","chicago":"Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and Scale in Vertebrate Spinal Cord Development.” Wiley Interdisciplinary Reviews: Developmental Biology. Wiley, 2021. https://doi.org/10.1002/wdev.383.","apa":"Kuzmicz-Kowalska, K., & Kicheva, A. (2021). Regulation of size and scale in vertebrate spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology. Wiley. https://doi.org/10.1002/wdev.383","ama":"Kuzmicz-Kowalska K, Kicheva A. Regulation of size and scale in vertebrate spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology. 2021. doi:10.1002/wdev.383","short":"K. Kuzmicz-Kowalska, A. Kicheva, Wiley Interdisciplinary Reviews: Developmental Biology (2021).","ieee":"K. Kuzmicz-Kowalska and A. Kicheva, “Regulation of size and scale in vertebrate spinal cord development,” Wiley Interdisciplinary Reviews: Developmental Biology. Wiley, 2021.","mla":"Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and Scale in Vertebrate Spinal Cord Development.” Wiley Interdisciplinary Reviews: Developmental Biology, e383, Wiley, 2021, doi:10.1002/wdev.383."},"month":"04","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology. The formation and sculpting of organs begins during embryonic development. As it develops, the spinal cord extends in anterior–posterior direction in synchrony with the overall growth of the body. The dorsoventral (DV) and apicobasal lengths of the spinal cord neuroepithelium also change, while at the same time a characteristic pattern of neural progenitor subtypes along the DV axis is established and elaborated. At the basis of these changes in tissue size and shape are biophysical determinants, such as the change in cell number, cell size and shape, and anisotropic tissue growth. These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern."}],"ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"14323","status":"public"}]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"8800","checksum":"f0a7745d48afa09ea7025e876a0145a8","success":1,"date_updated":"2020-11-24T13:11:39Z","file_size":2527276,"creator":"dernst","date_created":"2020-11-24T13:11:39Z","file_name":"2020_WIREs_DevBio_KuzmiczKowalska.pdf"}],"publication_status":"published","publication_identifier":{"eissn":["17597692"],"issn":["17597684"]},"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","_id":"7883","department":[{"_id":"AnKi"}],"file_date_updated":"2020-11-24T13:11:39Z","ddc":["570"],"date_updated":"2024-03-07T15:03:00Z"}]