Transcriptional control of long-range cortical projections.

Long-range projection neurons of the neocortex form the major tracts of the mammalian brain and are crucial for sensory-motor, associative and executive functions. Development of such circuits involves neuronal proliferation, specification and migration, as well as axonal elongation, navigation and targeting, where growing axons encounter multiple guidance cues and integrate these signals to execute guidance decisions. The complexity of axon guidance mechanisms in the formation of long-range neuronal projections has suggested that they might be under control of transcription factors, which are DNA-binding proteins that regulate the expression of downstream genes. Here we discuss recent advances in our understanding of the control of axon guidance by transcriptional regulation, as well as future directions for the elucidation of the mechanisms and pathological relevance of this process.