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When size matters: CHD8 in autism

Nature Neuroscience volume 19, pages 1430–1432 (2016)Cite this article

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Recent models studying loss of the mouse homolog of the autism-associated gene CHD8 show altered Wnt signaling, cell fate and proliferation. How do these findings shape our understanding of this disease?

Among de novo mutations, CHD8 makes the single biggest known contribution to autism spectrum disorders (ASD). Previous work suggests that the protein functions at the center of a complex network of autism genes1. Encoding chromodomain helicase DNA-binding protein 8, CHD8 acts as a transcriptional repressor by remodeling chromatin structure and recruiting histone H1 to target genes. This supposed function as a 'puppet master' pulling the transcriptional strings of disease-relevant pathways makes it an attractive target in tackling one major question: is there a common underlying mechanism for ASD? In this issue of Nature Neuroscience, Durak et al.2 address this question by employing in utero knockdown of the mouse homolog Chd8. They found that Chd8 depletion during the neurogenic period shifts the balance toward the production of neurons at the expense of progenitor cells. Adult mice exhibited social behavior deficits reminiscent of those in subjects with CHD8 mutations. Such abnormalities have also been reported in a recently published study by Katayama and colleagues employing a haploinsufficient engineered mouse model3.

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Figure 1: Schematic overview of the genetic origin and functional impact of Chd8 and CHD8 loss in the paper by Durak et al.2 (left column), human subjects (middle column)14 and the paper by Katayama et al.3 (right column).

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Authors and Affiliations

  1. Martin W. Breuss and Joseph G. Gleeson are in the Department of Neurosciences, Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, University of California, San Diego, La Jolla, California, USA.,

    Martin W Breuss & Joseph G Gleeson

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  1. Martin W Breuss
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  2. Joseph G Gleeson
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Correspondence to Joseph G Gleeson.

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Breuss, M., Gleeson, J. When size matters: CHD8 in autism. Nat Neurosci 19, 1430–1432 (2016). https://doi.org/10.1038/nn.4431

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