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A central challenge in the genetics of autism spectrum disorders (ASDs) is advancing from gene discovery to the identification of actionable biological mechanisms. To investigate the function of ten genes that are strongly associated with ASD in the developing vertebrate brain, we performed behavioral, whole-brain structural, circuit, cellular and molecular analyses in zebrafish mutants of ASD genes. First, we identified both unique and overlapping effects of gene loss of function on basic sensory processing and arousal behaviors. Next, we identified the forebrain as the most significant contributor to brain size differences, while brain regions involved in sensory motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Third, using whole-brain RNA sequencing in zebrafish mutants of SCN2A and DYRK1A, we identified conservation of dysregulated pathways associated with ASD gene loss of function in zebrafish and mammals. Using hypothesis-driven gene set enrichment analysis, we found that dopaminergic genes are significantly enriched among downregulated genes in both mutants, while microglial genes are significantly enriched among upregulated genes. Finally, we show that both mutants display a significant increase in microglia throughout the brain, with DYRK1A mutants exhibiting a nearly two-fold increase in microglia. Therefore, our study implicates neuroimmune dysfunction as an important pathway downstream of select ASD genes. As a next step, we are using pharmaco-behavioral profiling to identify pharmacological suppressors of mutant behavioral phenotypes. Together, this study demonstrates the power of in vivo functional analyses in zebrafish to identify biologically relevant pathways downstream of ASD genes. [ABSTRACT FROM AUTHOR]