A Critical Role of GIT1 in Vertebrate and Invertebrate Brain Development.

GIT1, a multifunctional signaling adaptor protein, is implicated in the development of dendritic spines and neuronal synapses. GIT1 forms a signaling complex with PIX, RAC, and PAK proteins that is known to play important roles in brain development. Here we found that Git1-knockout (Git1(-/-) ) mice show a microcephaly-like small brain phenotype, which appears to be caused by reduced neuronal size rather than number. Git1(-/-) mice also show decreased dendritic spine number without morphological alterations in the hippocampus. Behaviorally, Git1(-/-) mice show impaired motor coordination and learning and memory. In addition, adult dGit Drosophila mutants show decreased brain size and abnormal morphology of the mushroom body. These results suggest that GIT1 is important for brain development in both rodents and flies.