Chromatin remodeller CHD7 is required for GABAergic neuron development by promoting PAQR3 expression.

ABSTRACT: Mutations in the chromatin remodeller-coding gene CHD7 cause CHARGE syndrome (CS). CS features include moderate to severe neurological and behavioural problems, clinically characterized by intellectual disability, attention-deficit/hyperactivity disorder and autism spectrum disorder. To investigate the poorly characterized neurobiological role of CHD7, we here generate a zebrafish chd7^-/- model. chd7^-/- mutants have less GABAergic neurons and exhibit a hyperactivity behavioural phenotype. The GABAergic neuron defect is at least in part due to downregulation of the CHD7 direct target gene paqr3b, and subsequent upregulation of MAPK/ERK signalling, which is also dysregulated in CHD7 mutant human cells. Through a phenotype-based screen in chd7^-/- zebrafish and

SUBMITTER: Jamadagni P 

PROVIDER: S-EPMC8183419 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature