R.E. Bell Lecture

Wiring the brain: the molecules and mechanisms of neuronal guidance

Marc Tessier-Lavigne

Rockefeller University

The functioning of the brain is dependent on the billions of connections among nerve cells that are formed during embryonic development to establish the neuronal circuits that underlie all brain functions - perception, the control of movement, memory, consciousness. To generate these connections, neuronal growth cones must navigate over long distances through the embryonic environment along specific pathways to find their correct targets, guided by attractive and repulsive guidance cues. These guidance mechanisms act simultaneously and in coordinate fashion to direct pathfinding, and are mediated by mechanistically and evolutionarily conserved ligand-receptor systems. This presentation will describe some recent advances in elucidating neuronal growth and guidance mechanisms, including evidence that defects in these mechanisms underlie some human neurological disorders, and discuss mounting evidence that molecules that regulate neuronal guidance during development also contribute to wiring other tissues and organs and to regulating nerve regeneration following injury in the adult nervous system.