Albert Basson and his colleagues at King’s College London plan to study the function of the CHD8 gene in brain development. CHD8, which encodes a protein that changes the structure of chromatin, has emerged as one of the most significant autism-associated genes. In vitro studies — studies conducted in an external environment — have suggested that CHD8 might function as a regulator of the developmentally important WNT signalling pathway, but whether this activity is relevant to CHD8 function during brain development is not known.
In collaboration with Robert Knight at King’s College London, the researchers hope to generate zebrafish with reduced or absent CHD8 function to determine the function of CHD8 during brain development. They aim to use the zebrafish model to explore different hypotheses relating to CHD8 function. For example, they plan to employ genetic experiments to determine whether WNT pathway hyperactivation is responsible for disrupted brain development in CHD8 mutant fish.
The availability of a zebrafish model could allow researchers to rapidly test other mechanistic hypotheses to identify the critical mechanisms that underlie developmental anomalies associated with CHD8 dysfunction.