Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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Author: search.filters.author.Ozhan, GunesSubject: search.filters.subject.Zebrafish

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  • Article
    Notum1a Inhibition Promotes Neurogenesis in the Adult Zebrafish Brain
    (Nature Portfolio, 2025) Kocagoz, Yigit; Erdogan, Nuray Sogunmez; Ozdinc, Sevval; Ipekgil, Dogac; Katkat, Esra; Ozhan, Gunes
    Notum is a carboxylesterase enzyme that modulates extracellular signaling by hydrolyzing palmitoleoyl residues from proteins, thereby influencing key pathways involved in cell differentiation, survival, and proliferation. While notum1 expression has been identified in the brain, its role in adult neurogenesis remains poorly understood. Using the adult zebrafish brain as a model system, we demonstrate that the notum1a homolog is broadly expressed across various brain cell types but is absent in undifferentiated radial glial cells. Pharmacological inhibition of Notum activity with the small molecule inhibitor ABC99 stimulates activation of radial glial cells, leading to increased neurogenesis. A BrdU pulse-chase assay confirms that ABC99-induced proliferation enhances the production of mature neurons. Despite Notum's established role in Wnt signaling, transcriptional analysis following ABC99 treatment reveals no sustained impact on Wnt pathway targets, suggesting that Notum may regulate neurogenesis through alternative mechanisms. Our findings highlight notum1a as a potential modulator of neural progenitor cell dynamics in the adult brain and suggest that targeting Notum could represent a novel therapeutic strategy for neurodegenerative conditions characterized by impaired neurogenesis.
  • Article
    Gypsophila Eriocalyx Roots Inhibit Proliferation, Migration, and Tgf-Β Signaling in Melanoma Cells
    (Walter de Gruyter GmbH, 2025) Azbazdar, Yagmur; Ozhan, Gunes; Helvacioglu, Selin
    Objectives: Melanoma is a highly malignant and serious form of skin cancer. In addition to the standard treatments, complementary approaches, including phytotherapy, are also used to alleviate symptoms and improve patient well- being. This study aims to investigate the anticancer effects of Gypsophila eriocalyx (GE), an endemic species from Türkiye, on melanoma cells. We set out to determine the efficacy of GE in inhibiting melanoma cell proliferation, migration, and growth, and to explore its underlying mechanisms. Methods: We examined the impact of GE on the prolifera- tion of two melanoma cell lines, Malme-3M and SK-MEL-28, and assessed its developmental toxicity in zebrafish em- bryos. Next, we evaluated GE’s influence on colony forma- tion and wound healing in melanoma cells, as well as its ability to induce apoptosis and affect the TGF-β/Smad signaling pathway, by measuring pathway reporter activity and target gene expression. Results: GE inhibited cell proliferation in melanoma cell lines at concentrations 104 to 488 times lower than those required for normal non-malignant L929 fibroblast cells. In zebrafish embryos, GE demonstrated developmental toxicity only at concentrations above 50 μg/mL. GE treatment significantly impaired the colony formation and wound healing abilities of melanoma cells, indicating reduced pro- liferation and migration. Moreover, GE induced apoptosis in melanoma cells and inhibited the TGF-β/Smad signaling pathway, as evidenced by decreased pathway reporter activity and target gene expression. Conclusions: This study highlights the potential of GE as a novel therapeutic agent in melanoma treatment by demon- strating its ability to inhibit tumor growth and progression
  • Article
    Citation - WoS: 1
    Citation - Scopus: 2
    <i>tubg1</I> Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model
    (Springer, 2024) Cark, Ozge; Katkat, Esra; Aydogdu, Ipek; Iscan, Evin; Oktay, Yavuz; Ozhan, Gunes
    Development of the multilayered cerebral cortex relies on precise orchestration of neurogenesis, neuronal migration, and differentiation, processes tightly regulated by microtubule dynamics. Mutations in tubulin superfamily genes have been associated with tubulinopathies, encompassing a spectrum of cortical malformations including microcephaly and lissencephaly. Here, we focus on gamma-tubulin, a pivotal regulator of microtubule nucleation encoded by TUBG1. We investigate its role in brain development using a zebrafish model with somatic tubg1 mutation, recapitulating features of TUBG1-associated tubulinopathies in patients and mouse disease models. We demonstrate that gamma-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between gamma-tubulin and canonical Wnt/beta-catenin signaling, with gamma-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that gamma-tubulin could be a potential target for further research in neurodevelopmental disorders, although challenges such as mode of action, specificity, and potential side effects must be addressed.