Dokument: Ecdysone steroid hormone remote controls epithelial expansion and cancer progression in the Drosophila intestine
| Titel: | Ecdysone steroid hormone remote controls epithelial expansion and cancer progression in the Drosophila intestine | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=70507 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250818-111216-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Zipper, Lisa [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Thomas Klein [Gutachter] Prof. Dr. Aberle, Hermann [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Inter-organ communication is an important mechanism that evolved with the transition from unicellular to multicellular organisms and is crucial throughout development and during adaptations to external conditions. The generation of offspring relies on several adaptations of the mother’s body to ensure proper development of the offspring. These adaptations are orchestrated by steroid hormones like oestrogens and include a size increase of the absorptive epithelium in the intestine to fit higher energy demands. Hormone-mediated intestinal re-sizing during pregnancy has already been shown in mice as well as the invertebrate model organism Drosophila melanogaster, but the detailed mechanisms which coordinate intestinal size adaptations remained unknown.
This thesis shows a role for the steroid hormone 20 hydroxy ecdysone (20HE) in re-sizing of the female Drosophila intestine. Two effectors, Ecdysone-induced protein 75B (Eip75B) and Crooked legs (Crol), have been identified that function downstream of systemic 20HE to locally control intestinal stem cell (ISC) behaviour. Upon mating and increased circulating 20HE levels Eip75B induces differentiation of ISC into epithelial enterocytes (EC) to ensure increased nutrient uptake. Crol and its human ortholog hZNF267 were shown to differentially affect ISC behaviour depending on the cell type. Within ISC, Crol/hZNF267 has an antiproliferative role by repressing cell cycle regulators String (Stg) and Cyclin-B (CycB). In EC, Crol/hZNF267 non-autonomously promotes ISC proliferation by inducing expression and secretion of mitogenic Wingless (Wg) ligand. Mathematical modelling proved the plausibility that these opposing roles of Crol on ISC behaviour can induce a stable intestinal size which depends on 20HE levels. In different tumour models Eip75B induces differentiation of tumour stem cells into postmitotic EC, whereas Crol/hZNF267 prevents tumour formation within the tumour cells and non-autonomously fuels tumour growth when expressed in surrounding EC. Together, the findings presented in this thesis describe an example of inter-organ communication involving a steroid hormone which is translated into different outputs with opposing effects on ISC behaviour. These local outputs ensure adaptations of the female intestine to changes in metabolic demands during the production of offspring and advance the understanding of mechanisms controlling organ size. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Genetik | |||||||
| Dokument erstellt am: | 18.08.2025 | |||||||
| Dateien geändert am: | 18.08.2025 | |||||||
| Promotionsantrag am: | 26.02.2025 | |||||||
| Datum der Promotion: | 22.07.2025 |
