Autosomal recessive primary microcephaly (MCPH) is a congenital disease characterized by reduced brain size which affects 2-12 cases per 10,000 live births in U.S. There are currently 27 genes related to the MCPH phenotype. Mutations in the Abnormal Spindle-like, Microcephaly Associated (ASPM) gene account for the majority of human MCPH cases; this gene has an ortholog in Drosophila, abnormal spindle (asp), that displays the same small brain phenotype. Although mitotic spindle defects have been proposed to be the major driver of asp mutant brains, previous work from our lab and others have shown that the etiology of MCPH is complex and that multiple cellular pathways likely contribute to this disorder. This likely reflects additional roles that Asp has during neurogenesis. To uncover these roles and identify new pathways involved in MCPH, we analyzed the transcriptional landscape of asp mutant brains across three key neurodevelopmental time points: neurogenesis (3rd instar larvae), neuronal tissue remodeling (mid-pupae), and neural homeostasis (adult). Differential expression analysis revealed that the most significant expression changes (>1,000 genes, F.C. >0.5, P-value <0.05) were observed during the neurogenic and homeostasis periods, suggesting that neural remodeling does not play a major role in shaping the asp MCPH phenotype. GO analysis revealed a number of enriched terms, including an upregulation of immune system (NF-ΚB, Toll) and stress-related MAPK pathways that were consistent between neurogenic and homeostasis stages. To functionally test whether these pathways contribute to the etiology of asp MCPH, we probed genetic interactions between asp and components of the NF-ΚB (rel) & Toll (dif) pathways. Brain size was partially restored in asp/rel and asp/dif double mutant animals, despite no rescue of the neuropil disorganization phenotype. These results suggest that the inflammatory response may partially contribute to the asp small brain phenotype through a growth control mechanism that is currently under investigation. We will also present ongoing studies functionally testing the importance of MAPK-stress related pathways in the etiology of asp MCPH.