Heads of Laboratories
President
Professor
Laboratory of Brain Development and Repair
marctl@rockefeller.edu
Dr. Tessier-Lavigne’s laboratory investigates how neural circuits in the brain form during embryonic development. It also studies nerve cell responses to injury and the mechanisms underlying nerve cell death with the goal of developing therapies for brain injury and neurodegenerative disease.
The human brain comprises several hundred billion nerve cells or neurons, which are connected in an intricate and precise pattern to form the neural circuits that underlie all brain functions, including perception, memory and the control of movement. These circuits form during embryonic development when each neuron sends out a slender extension, the axon, which seeks out and connects to an appropriate set of target cells. Dr. Tessier-Lavigne’s laboratory is interested in how these neuronal axons locate their targets during development. They also study how to stimulate the regeneration of neuronal connections after trauma such as stroke or spinal cord injury, and the mechanisms underlying the loss of connections and death of neurons in neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases.
In the embryonic brain, developing axons are tipped by a specialized sensory structure called the growth cone, which senses chemical guidance cues that instruct it to migrate in particular directions. The lab has discovered a number of the chemical cues operating in the mammalian nervous system, including small protein families known as netrins and slits, as well as receptors on the growth cones that detect many of these cues. To understand how guidance cues collaborate to ensure that the axons are guided unerringly, Dr. Tessier-Lavigne’s lab is seeking to identify the full complement of cues guiding particular sets of axons, as well as the intracellular pathways they trigger to signal directed motion. As an axon progresses along its trajectory, its growth cone exhibits a remarkable plasticity, changing its response to guidance cues — losing responsiveness to those that directed it over the previous leg of its trajectory, and acquiring responsiveness to those that will guide it over the next leg. A major focus in the lab is on understanding the mechanisms that control this plasticity and switching of growth cone responses, and their relation to other plastic changes, such as those occurring after injury and in learning and memory.
The mechanisms that direct the formation of connections in the embryo also regulate neuronal responses to injury in the adult. While damaged axons in the peripheral nervous system can regrow and regenerate connections, in the central nervous system — the brain and spinal cord — they cannot, and paralysis after spinal cord injury is usually permanent. Dr. Tessier-Lavigne’s lab has recently found that some of the cues that guide axons in the embryo contribute to blocking regeneration, and that inhibiting their actions can help stimulate repair.
The mechanisms regulating the development of circuits are also relevant to neurodegenerative disease. In the embryo, too many connections are initially formed, and many axons have to be eliminated through a process of pruning or developmental degeneration. Dr. Tessier-Lavigne’s lab has shown that several of the cues that initially guide axons are later responsible for triggering axon degeneration in the embryo, and that there are important mechanistic similarities between developmental degeneration and the degeneration that occurs in diseases like Alzheimer’s, providing potential therapeutic entry points for these diseases.
CAREER
Dr. Tessier-Lavigne received undergraduate degrees from McGill University and Oxford University, where he was a Rhodes Scholar. He received a Ph.D. in neurophysiology from University College London in 1987, and performed postdoctoral work at University College London and at Columbia University. From 1991 to 2003, he held faculty positions at the University of California, San Francisco, and at Stanford University, where he was the Susan B. Ford Professor in the Humanities and Sciences. He was also an investigator with the Howard Hughes Medical Institute. He joined Genentech, a leading biotechnology company, in 2003 and was promoted to executive vice president for research and chief scientific officer in 2009. He joined Rockefeller as president and professor in March 2011.
Dr. Tessier-Lavigne is a member of the National Academy of Sciences, a fellow of The Royal Society, a fellow of The Royal
Society of Canada, a fellow of the Academy of Medical Sciences (UK) and a fellow of the American Association for the
Advancement of Science. He is the recipient of numerous awards, including the Ameritec Prize for contributions towards a cure for
paralysis, the Ipsen Foundation Prize in Neuronal Plasticity, the Viktor Hamburger Award of the International Society for
Developmental Neuroscience, the Wakeman Award for regeneration research, the Robert Dow Neuroscience Award, the Reeve-
Irvine Research Medal, the Gill Distinguished Award in Neuroscience and the W. Alden Spencer Award.
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