Abstract
De novo mutations of SYNGAP1 (Synaptic GTPase Activating Protein) have been found in human patients with intellectual disability, epilepsy and autism. Consistent with an important role for SYNGAP1 in nervous system development, mice heterozygous for SYNGAP1 loss-of-function mutations exhibit disrupted behavior and cognition. Studies in mice have focused on the role of SYNGAP1 at excitatory post-synapses even though SYNGAP1 is expressed prior to synaptogenesis. To study the potential roles of SYNGAP1 during early developmental stages, we carried out a syngap1 morpholino study in zebrafish and found that knockdown of syngap1 causes reduced brain size, increased cell death in the brain and spinal cord before synaptogenesis and disrupted behaviors. We also found decreased GABAergic precursors in syngap1b morphants and increased apoptosis in the GABAergic progenitor area. These findings bridge the gap between embryonic mutations and later phenotypes, supporting the emerging view of prenatal origin in etiology of neurodevelopmental disorders associated with autism spectrum disorders.