--- OA_place: publisher _id: '14323' 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. acknowledged_ssus: - _id: Bio - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarzyna full_name: Kuzmicz-Kowalska, Katarzyna id: 4CED352A-F248-11E8-B48F-1D18A9856A87 last_name: Kuzmicz-Kowalska citation: 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 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 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. 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. 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. 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. corr_author: '1' date_created: 2023-09-13T10:07:18Z date_published: 2023-09-13T00:00:00Z date_updated: 2026-04-14T09:50:54Z day: '13' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: AnKi doi: 10.15479/at:ista:14323 file: - access_level: open_access checksum: bd83596869c814b24aeff7077d031c0e content_type: application/pdf creator: kkuzmicz date_created: 2023-09-13T09:52:52Z date_updated: 2025-03-13T23:30:05Z embargo: 2025-03-13 file_id: '14324' file_name: PhDThesis_KK_final_pdfA.pdf file_size: 10147911 relation: main_file - access_level: closed checksum: aa2757ae4c3478041fd7e62c587d3e4d content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: kkuzmicz date_created: 2023-09-13T09:53:29Z date_updated: 2025-03-13T23:30:05Z embargo_to: open_access file_id: '14325' file_name: thesis_KK_final_corrections_092023.docx file_size: 103980668 relation: source_file file_date_updated: 2025-03-13T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '151' project: - _id: 267AF0E4-B435-11E9-9278-68D0E5697425 name: The role of morphogens in the regulation of neural tube growth publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7883' relation: part_of_dissertation status: public status: public supervisor: - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 title: Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ...