The correct wiring of neurons within the human nervous system, and the resulting brain function and behavior, depend on one of the most difficult navigational challenges in biology. Remarkably the pattern of connections is well-preserved from person to person, and mis-wiring of these connections is associated with complex brain disorders. Thus the genetically dictated instructions for wiring the brain are followed accurately by a specialized navigational growth cone structure at the tip of each extending axon. Over the last 25 years, the extracellular cues and receptors on the growth cone surface that promote faithful axon guidance have been identified. Similarly, how the cytoskeleton produces the force to move the growth cone forward is fairly well understood. However how extracellular cues are translated into to changes in the intra-cellular cytoskeleton has not been understood. The Gupton lab identified the brain-enriched enzyme TRIM9 as a critical catalytic component that links the receptor of an attractive guidance cue to cytoskeletal regulators critical for axon guidance in neurons. Further they found that loss of TRIM9 resulted in malformed nerve fibers in the intact mouse brain. A more complete understanding of how the nervous system is wired during development and the identification of the factors that are critical for achieving this will improve our understanding of normal development as well as complex brain disorders.
To view the whole article, click here.