The Scolnick Prize is awarded annually by the McGovern Institute to recognize outstanding advances in the field of neuroscience.
“We congratulate Tom Jessell on this award,” says Robert Desimone, director of the McGovern Institute and chair of the selection committee. “He has been a pioneer in transforming developmental neuroscience from a descriptive to a mechanistic and molecular science.”
Jessell received his PhD from Cambridge University, and has held faculty appointments at Harvard Medical School and at Columbia University, where he is now the Claire Tow Professor of Neuroscience. He is also an investigator of the Howard Hughes Medical Institute.
Since moving to Columbia University in 1985, Jessell’s primary interest has been the embryonic development of the nervous system, specifically the spinal cord, which because of its relative simplicity and evolutionary conservation offers an ideal system for understanding general principles of neural development.
Jessell’s work has revealed the molecular mechanisms responsible for establishing the spatial organization of the spinal cord. He showed that the cord is shaped during embryonic development by diffusible signaling molecules known as “morphogens.” Two different classes of molecules are secreted by the most dorsal and ventral parts of the developing cord respectively, forming two opposing concentration gradients in the dorso-ventral axis. The concentrations of these signaling molecules provide “positional information” to embryonic cells, instructing them to differentiate in ways that are appropriate for their specific locations within the cord.
Jessell has also studied the molecular mechanisms by which developing cells respond to positional signals. Spinal motor neurons, for example, are known to cluster into “pools,” groups of neurons that form at stereotypic locations within the ventral spinal cord and which innervate a common target muscle. There are at least 50 different muscles in a vertebrate limb, each of which must be correctly innervated to allow precise control of movement. Jessell has shown that the identities of different motor pools are specified by combinations of transcription factors which are activated in different spatial domains in response to positional cues. These transcriptional “master regulators” work by controlling the expression of downstream genes that determine the distinctive properties of different neurons, including their shapes, their biochemical and electrical properties, and their choice of peripheral and central connections.
The discovery of these genetic mechanisms has made it possible to identify and manipulate the activity of specific classes of neurons with great precision, and Jessell has used this approach to reveal the link between functional circuitry and motor behavior. In addition to fundamental questions, Jessell’s work has important practical implications for the emerging field of regenerative medicine. There is great interest in stem cells as a renewable source of cells for transplantation therapy, but for this approach to succeed, stem cells must be converted to the desired cell type. Jessell’s work on transcriptional control of neural identity provides a roadmap for such efforts, and he has demonstrated its feasibility in the case of spinal motor neurons, which degenerate in diseases such as amyotrophic lateral sclerosis. In collaboration with his former postdoc Hynek Wichterle, Jessell recently showed that embryonic stem cells can be induced to form a wide variety of motor neuron subtypes, and that when these neurons are transplanted into host embryos they can settle at the correct locations in the spinal cord and form appropriate axonal projections toward their normal targets. The implications of this result go well beyond motor neuron diseases; many disorders of the nervous system affect particular cell types, and the ability to convert stem cells to specific classes of neurons may eventually find wide applications in clinical neuroscience.
In addition to his many research contributions, Jessell also had great influence as a teacher and mentor. He is a coauthor of the classic textbook Principles of Neural Science, now in its fifth edition, and he has trained dozens of students and postdocs, many of whom are now recognized leaders in the field of neural development. Among the most notable is Marc Tessier-Lavigne, now president of Rockefeller University, whose pioneering work on the molecular basis of axon guidance was begun during a postdoctoral fellowship in Jessell’s lab.
The McGovern Institute will award the Scolnick Prize to Dr Jessell on Monday April 1, 2013. At 4.00 pm he will deliver a lecture entitled “Sifting Circuits for Motor Control,” to be followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar Street (building 46, room 3002) in Cambridge. The event is free and open to the public.