Skip to main content


Table 1 Summary of the findings from the current study and relevant literature

From: Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons

Reference(s) Endogenous CHD8 expression data relating to the current study Model system(s) and method(s) used for disrupting CHD8 expression Findings caused by disrupting CHD8 expression relating to the current study
Current study Human (Brodmann region 19): CHD8 expressed in astrocytes (GFAP+) and in neurons (MAP2+, PV+, DCX+) by immunohistochemical stains
Mice (whole brain lysates): CHD8 expression peaks at E16-E18, decreases substantially postnatally by qPCR and western blotting
Mice (P3 brain sections and cultured neurons): CHD8 expression shows nuclear localization in MAP2+ neurons by immunostaining
Mice (cultured neurons and glia): CHD8 is expressed in cultured neurons and to a lesser extent in cultured glia by western blotting
Mice (in vitro)—cultured neurons transfected with Chd8 shRNA constructs
Mice (in vivo)—in utero electroporation at E14.5 with Chd8 shRNA constructs
Decreased axon length (both in vitro and in vivo)
Reduced dendritic complexity (both in vitro and in vivo)
Delayed neuronal migration (higher percentage of GFP+ cells in VZ/SVZ instead of CP) at E18.5 (in vivo), which normalized by P3
Durak et al. [18] Mice (brain lysates): expression peaks at E12, then decreases during embryonic development to P2 by qPCR
Human (DFC and MFC): expression peaks during early-mid fetal development and decreases from late fetal development to childhood by qPCR
Mice—in utero electroporation at E13 (for neuronal proliferation/migration studies) or E15 (for dendritic arborization studies) with Chd8 shRNA constructs Increased neuronal migration (more GFP+ cells in CP instead of VZ/SVZ) at E16, accompanied by reduced proliferation, increased cell cycle exit, reduced mitotic activity, and premature Tuj1 expression
Decreased dendritic arborization in upper cortical neurons from 5-month-old mice
CHD8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling
Nishiyama et al. [20] and Katayama et al. [21] Mice (whole embryos): CHD8 was expressed in ES cells (~E3.5), E8.5 embryos, E12.5 embryos, E16.5 embryos, and to a lesser extent in newborn pups by western blotting Mice—two lines of germline haploinsufficient mice were generated (replacing 9 exons with loxP-neo cassette, or ∆exons 11–13, disrupting only the long protein isoform) Homozygous mutants show massive apoptosis at E7.5 and lethality
At E14.5, haploinsufficient mice showed increased expression of early-fetal genes and decreased expression of mid-fetal genes
Platt et al. [22] Mice (whole brains): expression profile from E10-P0, adult. Expression is highest at E10 and decreases over development by western blotting
Mice (adult brain sections, somatosensory cortex): CHD8 shows nuclear localization and co-expresses with NeuN, PV, CNP1, and GFAP by immunostaining
Mice—germline haploinsufficient mice were generated by CRISPR/Cas9 introducing a 7 nucleotide deletion in exon 1, which disrupted the expression of both CHD8 isoforms Normal lamination and specification of neuronal cell types at P21
No difference in number of cortical progenitor cells or cell cycle length at E15.5
Zhao et al. [25] Mice (P14 white matter tracts): CHD8 is expressed in oligodendrocytes and to a lesser extent in GFAP+ astrocytes by immunostaining
Human (cerebellum): CHD8 expression in Sox10+ oligodendrocytes by immunostaining
Mice (P14 cortical sections): CHD8 is expressed in NeuN+ neurons but not clearly in GFAP+ astroctyes or Iba1+ microglia by immunostaining
Conditional Chd8 knockout mice (loxP sites surrounding exon 4) crossed with oligodendrocyte-specific Cre line Homozygous conditional knockout mice show lethality by P21 and myelination defects
Homozygous conditional knockout mice show reduced proliferation of oligodendrocyte precursor cells in P1 spinal cord
Dual requirement of CHD8 for chromatin landscape establishment and histone methyltransferase recruitment to promote CNS myelination and repair
Gompers et al. [35] Expression analysis was not reported for different cell types or developmental time points Mice—germline Chd8 haploinsufficient mice were generated (deletion of exon 5) Increased proliferation of neuronal progenitors at E14.5
No gross lamination errors by P0 and P7
Wang et al. [36]
CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment
N/A CRISPR/Cas9-mediated heterozygous knockout of CHD8 in iPSCs Genes involved in cell cycle, neuronal differentiation, and in neuronal projection development are dysregulated
Suetterlin et al. [23] N/A Chd8+/− mice (loxP sites on exon 3) crossed β-actinCre line Chd8 heterozygous mice display increased total brain volume and showed volumetric increased of several brain regions, including cortical areas, hippocampus and parts of the cerebellum by high-solution MRI
CHD8 controls the expression of ASD-associated axon guidance genes in the early postnatal neocortex
Jung et al. [24] In both males and females, CHD8 protein was more abundant in the brain relative to other tissues, at embryonic stages relative to postnatal stages, and in non-crude synaptosomal fractions Chd8+/N2373 K mice carrying a heterozygous Chd8 frame-shift mutation Distinct c-fos signals in male and female Chd8+/N2373K brains under baseline and maternal-separation conditions
Opposite changes in inhibitory synaptic transmission in the male and female Chd8+/N2373K hippocampus