 Increasing evidence suggests many neurological disorders are the result of developmental disruptions, such as circuits or cells in the brain not reaching full maturity. Just as entire organisms go through a developmental process, so too do their individual cells. Microglia are a type of immune cell found in the brain and spinal cord that play an important role in neurodevelopment. As such, these cells have been implicated in numerous neurological disorders, from Alzheimer's to autism, the incidences of which differ between males and females. However, the mechanisms underlying microglial development and their possible role in sex differences in these disorders are not yet fully understood. To provide insights into this, a team of researchers at Harvard, University of Pennsylvania and Duke University developed a strategy to analyze and identify gene expression patterns of mouse microglia across development. Microglia were isolated from the hippocampus of male and female mice at different developmental stages, ranging from embryonic day 18 to postnatal day 60. Using next-generation RNA sequencing, the team created a microglial developmental index, or MDI, involving thousands of genes whose expression levels changed significantly throughout development. Despite the prohibitively large amount of data present in transcriptomes, this index allowed the researchers to efficiently analyze microglial gene expression data from whole transcriptomes. They found that the gene expression program in males is delayed relative to females during early adolescence. During this discrepancy in development, male microglia are more sensitive to immune stimuli than female microglia, which may explain the sex biases in some neurological disorders. This was validated by changes in cell morphology. To further test the usefulness of the MDI, the researchers applied it to human subjects, which consisted of diseased and non-diseased postmortem brain samples. Unlike laboratory mice, humans are exposed to several environmental challenges such as infections during development. Significantly, the research team determined that microglial development progressed much more rapidly in normal adult males compared to females, likely due to these challenges. Additionally, microglial development was significantly accelerated in brain tissue samples from autism and Alzheimer's patients compared to age-matched controls, suggesting that accelerated development of microglia, rather than inflammation per se, contributes to neuropathology. The novel index generated in this study has broad applicability, giving future researchers a powerful tool to examine microglial development and provide further insights into devastating neurological disorders.