Marc Tessier-Lavigne
Born into a Canadian military family, Marc Tessier-Lavigne moved several times during his childhood, living in Great Britain and Belgium, as well as in Canada. Mathematics was his favorite subject in school, although he also enjoyed science classes. “I loved the history of science, and spent a lot of time reading about scientists,” he recalls. Tessier-Lavigne majored in physics at McGill University, graduating in 1980 at the age of 20. He then went to Oxford University as a Rhodes scholar, where he double-majored in philosophy and physiology. “It was perfect,” he says. “The philosophy taught me how to think, and the physiology gave me my vocation as a neuroscientist.”
Tessier-Lavigne received his PhD from University College London, where he did research in the lab of David Attwell, studying how neural circuits in the retina worked. “While studying neural function, I became fascinated with how these circuits could rise with such precision during embryonic development,” Tessier-Lavigne says. It was not until he took a course in developmental neurobiology at the Cold Spring Harbor Laboratory in New York, however, that he found the direction for his future work. “I determined then and there to pivot and work on brain development—not on how circuits work, but on how they form,” he says.
Tessier-Lavigne went to the Columbia University labs of Thomas Jessell and Jane Dodd to perform postdoctoral research on the embryonic development of spinal cord neurons. It was there that Tessier-Lavigne began his pioneering work on axon guidance. He and his colleagues reconstructed in vitro how commissural neurons (neurons whose axons cross to the opposite side of the spinal cord) target the spinal cord’s midline floorplate, showing that the floorplate secrets a chemical attractant that draws the commissural axons to it. He then turned his attention to identifying that attractant factor, a goal he pursued even more intensely after setting up his own lab at the University of California, San Francisco. “I thought it was the single most important and exciting thing I could do,” he recalls. “At that point, not a single axon guidance cue had been identified in any organism.”
In 1994, after three years of research involving more than 25,000 embryonic chick brains, Tessier-Lavigne and his colleagues announced in the journal Cell the discovery of axonal chemical attractants in the spinal cord, which they called Netrins (from the Sanskrit netr, meaning “one who guides”). That finding marked a giant step forward in the understanding of how neurons navigate the embryonic environment to locate their targets. It also revealed a remarkable and unexpected conservation of guidance mechanisms across evolution, since Netrins were also independently identified in nematode worms. During the next decade-and-a-half, at his labs at UCSF and, after 2001, at Stanford University, Tessier-Lavigne published a series of groundbreaking papers that further elucidated the molecular mechanisms that control axon guidance. He showed, for example, that an additional chemical attractant, Sonic hedgehog (Shh), collaborates with Netrins in the spinal cord floorplate to facilitate axon guidance, and that a repellent, NELL2, further collaborates with those attractants by helping prevent the axons from straying from their path. Other major discoveries included the purification in vertebrates of the Slit family of proteins, which stimulate the growth and branching of sensory neuron axons, and also function to enable commissural axons that reach the spinal cord midline to move on by repelling them. That finding was soon followed by the identification of the vertebrate Roundabout (Robo) receptors that mediate the actions of Slit proteins. He also identified vertebrate receptors for Netrins and for Semaphorins, as well as a series of other chemoattractants for sensory axons and motor axons. During this remarkably prolific period of advancements in the field of axon guidance, Tessier-Lavigne, who was working primarily with mammals, often co-published with his University of California, Berkeley, colleague Corey Goodman, who was working in insects, as the two collaborated to investigate related axon guidance mechanisms. Their work helped rapidly drive the field forward and establish that the molecules involved in guiding commissural axons are highly conserved throughout the animal kingdom.
In 2003, Tessier-Lavigne left academia to become an executive with the biotechnology company Genentech, Inc. He saw the move as an opportunity to focus on translational research—taking discoveries from the lab and moving them into clinical settings. At Genentech, Tessier-Lavigne eventually directed 1,400 researchers, and helped oversee the development of multiple groundbreaking drugs for cancer, immune and other disorders, eight of which have been approved by the FDA. “I have always been very excited about supporting other scientists to do their best work,” he says. “I get as much gratification out of that as I do from my own science.” By 2011, however, Tessier-Lavigne believed he might have a bigger impact on neuroscience and therapeutics if he returned to academia. That year he become president of Rockefeller University, and since 2016, has held the same position at Stanford University.
Even as he has assumed these various leadership roles in the private and academic sectors, Tessier-Lavigne has retained a lab and remained active in neuroscience research. Currently, in addition to continuing his studies of axon guidance, he also focuses on the molecular mechanisms of axon degeneration, and of axonal plasticity in the adult brain.
Tessier-Lavigne has received numerous honors and awards during his career, including memberships in the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences and the American Philosophical Society, as well as the Fondation IPSEN prize for “axon guidance” with Friedrich Bonhoeffer and Corey Goodman. He has also mentored and trained many graduate and postdoctoral students who are now recognized leaders in neuroscience research at academic institutions around the world. Tessier-Lavigne is married to Mary Hynes, a noted neuroscientist whose research focuses on Parkinson’s disease. She is currently a research associate professor of biology at Stanford University. The couple has three grown children.