Jamadagni, Priyanka; Breuer, Maximillian; Samarut, Eric et Patten, Shunmoogum A. . Understanding the role of chromatin remodeler chd7 in GABAergic network development using a zebrafish loss-of function model In: 11e European Zebrafish Meeting, 26-27 October 2020, virtuel.
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Mutations in the ATP-dependent chromatin remodeller chromodomain, helicase, DNA binding (CHD) 7 are the primary cause of CHARGE syndrome and have been associated with autism spectrum disorder (ASD) . However, the mechanisms by which mutations in CHD7 affect brain development and function are poorly understood. We have developed a zebrafish chd7 CRISPR/Cas9 knockout model, employing the suitability of this vertebrate model for the study of early neurodevelopment. chd7 knockout zebrafish larvae exhibit a small head phenotype, defects in craniofacial cartilage development, heart defects and had no swim bladder. We also found that chd7-/- fish display aberrant axonal network development. Interestingly, the mutant fish displayed hyperactivity particularly during the dark phase of the light-dark cycle. Reports suggest, an aberrant inhibitory signaling in the brain could be a mechanism underlying this phenotype in a zebrafish model for ASD. Interestingly, treatment with the GABA-A receptor antagonist PTZ showed that chd7 mutants exhibit an increased sensitivity to PTZ-induced seizures. Further, we observed a significant decrease in GABAergic neurons in chd7 mutants, that in certain regions of the brain is due to a failure in the migration of these cells. Using an unbiased whole transcriptomic approach, genes involved in cell proliferation, migration and cell adhesion that are dysregulated in the chd7 mutants were identified. Our findings indicate loss of chd7 results in a deficit of inhibitory neurons, suggesting an essential role of chd7 in the brain neuronal network development.
| Type de document: | Document issu d'une conférence ou d'un atelier |
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| Informations complémentaires: | Affiche scientifique P176 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 14 juill. 2021 15:43 |
| Dernière modification: | 14 juill. 2021 15:43 |
| URI: | https://espace.inrs.ca/id/eprint/11859 |
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