Cortical neurons require Otx1 for the refinement of exuberant axonal projections to subcortical targets

Information processing in the nervous system depends on the creation of spe cific synaptic connections between neurons and targets during development. The homeodomain transcription factor Otx1 is expressed in early-generated n eurons of the developing cerebral cortex. Within layer 5, Otx1 is expressed by neurons with subcortical axonal projections to the midbrain and spinal cord. Otx1 is also expressed in the precursors of these neurons, but is loc alized to the cytoplasm. Nuclear translocation of Otx1 occurs when layer 5 neurons enter a period of axonal refinement and eliminate a subset of their long-distance projections. Otx1 mutant mice are defective in the refinemen t of these exuberant projections, suggesting that Otx1 is required for the development of normal axonal connectivity and the generation of coordinated motor behavior.