Joshua Sanes, the Jeff C. Tarr Professor of Molecular and Cellular Biology, emeritus, and founding director of Harvard’s Center for Brain Science (CBS), has spent his career exploring one of biology’s most intricate puzzles: how the billions of neurons in the brain find their correct partners and form the connections, called synapses, that underlie thought, movement, and perception.
Though his active research career has concluded, the influence of his work continues to shape neuroscience. Sanes’s discoveries—spanning from the molecular choreography of synapse formation to the diversity and organization of retinal neurons—have become cornerstones in understanding how the brain wires itself during development.
From Biochemistry to Brain Circuits
Sanes’s path to neuroscience began with a dual interest in molecules and minds. He graduated from Yale University in 1970 with degrees in biochemistry and psychology—an unusual pairing that foreshadowed his lifelong fascination with bridging biology and behavior. “It was there that my advisor challenged me to think about how molecular mechanisms could explain something as complex as the brain,” Sanes recalled. “I have been thinking about that ever since.”
Sanes pursued graduate studies at Harvard, turning to the development of the nervous system and earning his PhD in neurobiology in 1976. After completing his doctorate, Sanes took an unexpected detour from the lab. Drawn to public service and policy, he spent a year in Washington, DC, working for the U.S. Congress in the Office of Technology Assessment. “It was an interesting time,” he said. “I wanted to understand how science fits into society—how discoveries translate into decisions that affect people’s lives.”
Ultimately, the pull of neuroscience proved stronger than policy. “It was a great experience, but I never lost sight of the fact that what I loved most was the process of discovery itself,” he said. He returned to research as a postdoctoral fellow, first at Harvard and then at the University of California, San Francisco, immersing himself once again in developmental neurobiology.
Decoding Synaptic Specificity
Sanes launched his independent career at Washington University School of Medicine in St. Louis, where he joined the faculty in 1980. Over the next two decades, he established a pioneering research program that transformed understanding of synaptic development.
He investigated the neuromuscular junction—the point where a motor neuron contacts a muscle fiber—as a model for synapse formation. “The neuromuscular junction was a wonderful model system,” Sanes recalled. “It’s relatively simple and accessible, and it let us ask basic questions about how a neuron finds the right target and forms a synapse that can remain stable for decades yet change if it needs to.”
His investigations revealed the interplay of extrinsic and intrinsic factors that guide this process. Sanes and his colleagues identified key molecular cues that help motor neurons recognize their targets, establish contact, and fine-tune communication at the synapse. These discoveries illuminated not only the biology of this particular synapse but also general principles governing synaptic development throughout the nervous system.
During his 24 years at Washington University, Sanes trained generations of neuroscientists, built collaborative research networks, and began formulating the ideas that would guide the next phase of his career.
From Muscles to Vision
In 2004, Sanes returned to Harvard to continue his exploration of neural circuitry—this time tackling the issue of specificity—how each neuron connects to just the right partners. “This question has fascinated neuroscientists for over a century,” he said.
For these studies, Sanes focused on the retina, which offered a uniquely accessible window into the brain’s wiring: thin, laminated, and rich with distinct neuronal types arranged in precise patterns.
“What makes the retina so special is that it’s both part of the brain and optically accessible,” Sanes said. “You can see, manipulate, and record from individual cells, trace their connections, and relate structure directly to function.”
In a series of groundbreaking studies, Sanes and his team catalogued the extraordinary diversity of cell types in the retina, revealing dozens of distinct neuronal types—each with specific shapes, synaptic partners, and functions. They identified the molecules that guide axons and dendrites to the correct retinal layers, ensuring that connections form within the proper circuits.
The group also demonstrated how neurons space themselves across the retina in regular mosaics to evenly sample visual information, and how they avoid crossing their own paths through a phenomenon known as self-avoidance. Together, these discoveries established a molecular and developmental framework for understanding how visual circuits assemble with precision. “We were able to show that there’s a molecular logic to it,” Sanes explains. “Neurons use distinct combinations of surface molecules that act almost like a barcode to identify compatible partners.”
Over the last decade, he expanded these studies, using new methods to classify and characterize all of the over 100 neuronal types in the retina. This work not only facilitated studies of development but also led to new insights into the evolution of neurons and their responses to injury and disease.
“Our hope was always that by looking carefully at a few systems—in our case, the neuromuscular junction and retina—we could uncover general principles of how the brain is wired,” Sanes explained. “What we found was not just complexity, but a kind of beautiful logic to the connections.”
Building a Home for Brain Science
Sanes played a pivotal role as the founding director of Harvard’s CBS, where he served from its inception in 2004. When he arrived, neuroscience at Harvard was thriving but scattered across departments and schools. CBS provided a unifying home for faculty, students, and postdocs working to understand the brain from molecules to cognition.
“Building the Center was one of the most rewarding parts of my career,” Sanes said. “It was a chance to create a space where biologists, psychologists, computer scientists, and engineers could come together to tackle big questions that no single discipline could answer alone.”
Under his leadership, CBS became a hub for interdisciplinary collaboration, integrating tools from genetics, imaging, computation, and behavior to probe how neural circuits give rise to perception and thought. The Center helped seed many of Harvard’s current strengths in neuroscience and continues to foster connections across the life and physical sciences.
Mentorship and Continuing Influence
Colleagues and former trainees often describe Sanes as a scientist whose influence extends far beyond his publications. His mentorship—marked by curiosity, clarity, and generosity—has shaped a generation of neuroscientists now leading labs around the world.
“Science is a collective enterprise,” he emphasized. “Any recognition I’ve received reflects the creativity and persistence of the students and colleagues I’ve been lucky enough to work with. They pushed the work in directions I couldn’t have imagined.”
Sanes’s legacy also includes his commitment to fostering open, collaborative research environments. Many of his trainees carry forward his philosophy that rigorous experimentation and conceptual clarity are not mutually exclusive but mutually reinforcing.
The impact of Sanes’s work has been recognized through numerous honors, including election to the US National Academy of Sciences and the British Royal Society, and culminating most recently in the 2024 Gerard Prize from the Society for Neuroscience—the organization’s highest award. Recent Harvard recipients include Catherine Dulac and Michael Greenberg, who shared the honor in 2019.
“It’s their highest award, so I was both surprised and honored,” Sanes said. “It’s wonderful to see how far the field has come since I started—and to know that some of our early ideas helped pave the way.”
Even in retirement, Sanes remains active in the scientific community, advising, writing, and reflecting on how the field has evolved. “The questions that drew me to neuroscience are still the ones that excite me today,” he said. “How do you build a brain? How does it organize itself into circuits that perceive, decide, and act? We’ve made enormous progress, but the beauty is that there’s still so much left to discover.”
A Career Built on Curiosity
Looking back, Sanes views his trajectory—from Yale undergraduate to policy advisor, postdoc, professor, and institute builder—as shaped by one consistent force: curiosity. “I’ve always felt that one of the joys of science is that you’re never really done,” he reflected. “Each discovery opens a dozen new questions. What’s most satisfying is seeing the next generation take those questions further than we could have imagined.”
For Joshua Sanes, that enduring curiosity—paired with a deep respect for the collaborative nature of science—has defined a career that continues to illuminate how the brain builds itself, one connection at a time.
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