Chd8, or Chromodomain Helicase DNA-binding 8, is a transcriptional regulator expressed in nearly all cell types. It is involved in multiple cellular processes such as cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis [3]. Mutations in Chd8 are strongly associated with autism spectrum disorder (ASD), and its study via genetic models can help understand the underlying mechanisms.

CHD8 haploinsufficiency in human cerebral organoids disrupts neurodevelopmental trajectories, accelerating inhibitory neuron generation and delaying excitatory neuron generation, which may be related to patients' macrocephaly [1]. Disruptive CHD8 mutations in humans define a subtype of autism, and zebrafish with chd8 disruption recapitulate features like increased head size and gastrointestinal motility impairment [2]. CHD8 suppression in induced pluripotent stem cell-derived neural progenitors impacts histone H3K36me3 and RNA alternative splicing [4]. Adult ablation of Chd8 in astrocytes in mice attenuates reactive gliosis and neuroinflammation [5].

In conclusion, Chd8 is crucial for normal neurodevelopment. Its disruption, as studied in various models, is strongly linked to ASD and other related phenotypes such as macrocephaly, and may also be involved in processes like reactive gliosis and neuroinflammation. Understanding Chd8's function through these models provides insights into the mechanisms of neurodevelopmental diseases.