Spatial transcriptomics of the developing mouse brain immune landscape reveals effects of maternal immune activation and microbiome depletion.

Immune molecules and their cognate receptors are developmentally regulated in brain and dynamically expressed in the context of neurodevelopmental disorders. Despite the importance of immune molecules to brain wiring, a comprehensive map of the neuroimmune landscape is lacking in developing brain. Here we employed multiplexed in situ spatial transcriptomics to measure the expression of major immune ligands and receptors in developing mouse brain during mid and late gestation. Given the importance of maternal environment in shaping fetal neurodevelopment, we determined how embryonic neuroimmune landscape was altered after maternal immune activation (MIA) and maternal microbiome depletion. Our study revealed notable sex-specific patterns in gene expression and spatial architecture within developing brain. We observed changes in the CXCL12/CXCR7 chemokine network after MIA and microbiome depletion, suggesting a potential common mechanism underlying neural progenitor abnormalities. This resource underscores how the maternal environment programs precise regulation of immune molecules in developing brain, highlighting sex-specific vulnerability.