Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders

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PROJECT SUMMARY Neurodevelopmental disorders (NDDs), are increasingly recognized as originating from dysregulation of early brain development, which represents a window of vulnerability to environmental compounds. Environmental compounds may alter neurodevelopment via epigenetic mechanisms, which may not induce massive cell death, but change the brain function through their epigenetic effect on stem cell fate and lineage development. However, tools to systematically examine the epigenetic impact of environment on neurodevelopment are lacking. Here we employ Microscopic Imaging of Epigenetic Landscape (MIEL) to screen ToxCast Phase III chemical library (4700 compounds) and to characterize hits that alter epigenetic landscape of human neural precursors without inducing cytotoxicity. Recognizing environmental insults and understanding their mechanism of action will enable the development of regulations and guidelines aimed at avoiding such insults and the development of antidotes and protective agents when exposure is unavoidable.