Current and future applications of light-sheet imaging for identifying molecular and developmental processes in autism spectrum disorders

Autism spectrum disorder (ASD) is identified by a set of neurodevelopmental divergences that typically affect the social communication domain. ASD is also characterized by heterogeneous cognitive impairments and is associated with cooccurring physical and medical conditions. As behaviors emerge as the brain matures, it is particularly essential to identify any gaps in neurodevelopmental trajectories during early perinatal life. Here, we introduce the potential of light-sheet imaging for studying developmental biology and cross-scale interactions among genetic, cellular, molecular and macroscale levels of circuitry and connectivity. We first report the core principles of light-sheet imaging and the recent progress in studying brain development in preclinical animal models and human organoids. We also present studies using light-sheet imaging to understand the development and function of other organs, such as the skin and gastrointestinal tract. We also provide information on the potential of light-sheet imaging in preclinical drug development. Finally, we speculate on the translational benefits of light-sheet imaging for studying individual brain-body interactions in advancing ASD research and creating personalized interventions.