PUBLICATION
tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model
- Authors
- Cark, O., Katkat, E., Aydogdu, I., Iscan, E., Oktay, Y., Ozhan, G.
- ID
- ZDB-PUB-240902-3
- Date
- 2024
- Source
- Molecular neurobiology : (Journal)
- Registered Authors
- Aydoğdu, Ipek, Katkat, Esra, Özhan, Günes
- Keywords
- Neurodevelopmental disorder, Tubulin gamma 1, Tubulinopathies, Wnt/β-catenin signaling, Zebrafish
- MeSH Terms
-
- Mutation*/genetics
- Microcephaly/genetics
- Phenotype*
- Neurodevelopmental Disorders/genetics
- Neurodevelopmental Disorders/metabolism
- Neurodevelopmental Disorders/pathology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Brain/metabolism
- Brain/pathology
- Disease Models, Animal*
- Tubulin*/genetics
- Tubulin*/metabolism
- Animals
- Neurogenesis/genetics
- Wnt Signaling Pathway/genetics
- Zebrafish*/genetics
- PubMed
- 39215931 Full text @ Mol. Neurobiol.
Citation
Cark, O., Katkat, E., Aydogdu, I., Iscan, E., Oktay, Y., Ozhan, G. (2024) tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model. Molecular neurobiology. :.
Abstract
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 γ-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 γ-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between γ-tubulin and canonical Wnt/β-catenin signaling, with γ-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that γ-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping