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Thomas M. Jessell, PhD

Academic Appointments

  • Claire Tow Professor of Motor Neuron Disorders (in Neuroscience)

Current Administrative Positions

  • Co-Director, Mind Brain Behavior Initiative
  • Co-Director, Kavli Institute for Brain Science
Thomas M. Jessell, PhD

Thomas Jessell is an Investigator of the Howard Hughes Medical Institute, a Professor of Biochemistry and Molecular Biophysics and Neuroscience, and a member of the Neurobiology & Behavior doctoral program at Columbia University. Dr. Jessell received his Ph.D. in neuroscience from Cambridge University, UK, worked as a post-doctoral fellow at Harvard Medical School, and as a Locke Research Fellow of the Royal Society. In 1981 he became an Assistant Professor in the Department of Neurobiology at Harvard Medical School. In 1985 he moved to Columbia University as an Investigator of the Howard Hughes Medical Institute.

The Assembly and Organization of Sensory-Motor Circuits The task of assembling functional neural circuits is at its most challenging in the central nervous system, where hundreds of different neuronal types form thousands of synaptic connections, each with a selective subset of potential targets. We have been examining the developmental organization and function of neural connections through a focus on the spinal circuits involved in the control of movement.

Motor Neuron Diversity and Connectivity We are exploring the mechanisms that link neuronal identity and connectivity through an analysis of spinal motor neurons. Our recent work has shown that three classical features of organization of motor neurons that project to specific target muscles in the limb—their diversity, their stereotyped position, and their connectivity—are established by a Hox transcriptional regulatory network. These Hox interactions both constrain motor pools to specific rostrocaudal levels of the spinal cord and drive the diversification of motor neurons at a single segmental level. Moreover, this Hox regulatory network directs selective motor neuron connectivity with limb muscles. The output of this motor neuron Hox regulatory circuit is mediated through the expression of downstream transcription factors and surface molecules, which in turn direct target muscle connectivity and motor neuron sorting.

Sensory Feedback Connections with Motor Neurons The coordination of motor output depends critically on sensory feedback information provided by proprioceptive sensory neurons. The selectivity of proprioceptive afferent–motor neuron connectivity has its basis in the formation of distinct afferent termination zones in the spinal cord, as well as in the recognition of specific motor neuron targets. We have found that the specificity of proprioceptive axonal inputs to motor neurons is controlled by two main classes of transcription factors, Runx and ETS proteins. The level of Runx3 expression by sensory neurons is a primary determinant of the projection pattern of sensory axons within the spinal cord. These sensory transcription factors regulate sensory-motor connectivity, in part through expression of cell surface recognition proteins of the plexin and cadherin families. We are now examining how the selectivity of expression of these recognition proteins by sensory and motor neurons influences the formation and specificity of sensory-motor connections.

Dissecting Interneuron Circuits that Control Motor Behavior Interneurons have a major role in the coordination of motor behavior, but little is known about their organization, in part because of the difficulty in identifying and manipulating specific interneuron populations. We have identified transcription factors that define specific sets of spinal interneurons, each with a different intraspinal projection pattern and target connectivity. The selectivity of transcription factor expression permits a systematic assessment of the contribution of these neurons to specific motor behaviors, through the expression of toxin or channels that regulate the neural activity.  These studies are starting to reveal the core logic of local circuits that gate sensory-motor transmission and pattern motor output.

Departmental Appointments

  • Department of Biochemistry and Molecular Biophysics
  • Department of Neuroscience

Lab Locations

  • Hammer Health Sciences Building

    701 West 168th Street
    Room 1018
    New York, NY 10032
    Phone:
    (212) 305-1531
    Email:
    tmj1@cumc.columbia.edu

Honors & Awards

Investigator, Howard Hughes Medical Institute

Research Interests

  • Motor Systems
  • Synapses and Circuits
  • Axon Pathfinding and Synaptogenesis
  • Stem Cell Biology
  • Neurogenetics
  • Cellular/Molecular/Developmental Neuroscience

NIH Grants

  • LEVERAGING DYNAMICAL SMOOTHNESS TO PREDICT MOTOR CORTEX POPULATION ACTIVITY (Private)

    Jul 1 2017 - Jun 30 2022

    JUNIOR FELLOWSHIP OF THE SIMONS SOCIETY OF FE (Private)

    Jul 1 2017 - Jun 30 2020

    MOTOR CORTICAL CONTROL OF VOLUNTARY FORELIMB MUSCLE ACTIVITY (Federal Gov)

    Sep 1 2016 - Aug 31 2018

    DELINEATING CORTICO-SPINAL CIRCUITS FOR SKILLED MOTOR BEHAVIOR (Private)

    Jul 1 2016 - Jun 30 2018

    CADHERIN-CATENIN BASED RECOGNITION IN SENSORY-MOTOR CONNECTIVITY (Federal Gov)

    Sep 1 2013 - Jun 30 2018

    CONTROL OF MOTOR NEURON DIFFERENTIATION (Federal Gov)

    Sep 30 2010 - Jun 30 2018

    EXPLORING SPINAL INTERNEURON CIRCUITRY IN ALS (Private)

    Mar 1 2015 - Feb 28 2017

    THE FUNCTIONAL LOGIC OF INHIBITORY MICORICRUITS (Private)

    Jan 1 2015 - Dec 31 2016

    NEUROTROPHIN 3 AND REGULATION OF PROPRIOCEPTOR SUBTYPE IDENTITY AND CONNECTIVITY (Federal Gov)

    Sep 30 2014 - Aug 31 2016

    SENIORS FELLOW IN THE SIMONS SOCIETY OF FELLOWS (Private)

    Sep 1 2013 - Aug 31 2016

    CONTROL OF SKILLED FORELIMB MOVEMENTS BY CEREBELLAR FEEDBACK CIRCUITS (Federal Gov)

    Aug 1 2014 - Jul 31 2016

    THE MICROCIRCUITRY OF MOTOR CORTICAL FIRING DYNAMICS (Private)

    Apr 1 2013 - Mar 31 2016

    DEFINING MUTANT SOD1 ASTROCYTE MEDIATORS OF MOTOR NEURON TOXICITY (Private)

    Jul 1 2013 - Jun 30 2015

    BRAIN RESEARCH APPRENTICESHIPS IN NEW YORK AT COLUMBIA (BRAINYACS) (Private)

    Jan 1 2013 - Dec 31 2014

    SPINAL CIRCUITS FOR SKILLED FORELIMB MOVEMENT (Private)

    Apr 1 2011 - Mar 31 2014

    STUDIES ON INTERFERON-GAMMA INDUCED MOTOR NEURON DEGENERATION IN ALS (Private)

    Jan 1 2012 - Jun 30 2013

    GENETIC & GENE SPLICING, IPS DISEASE MODELING & DRUG SCREENING, AND MOTOR NEURON & GLIAL SIGNALING (Private)

    Jan 1 2010 - Jun 30 2013

    THE MOLECULAR LOGIC OF EMBRYONIC STEM CELL DERIVED MOTOR NEU RONS (NY State Gov)

    Jan 1 2009 - Dec 31 2011

    THE MOLECULAR LOGIC OF EMBRYONIC STEM CELL DERIVED MOTOR NEU RONS (NY State Gov)

    Jan 1 2009 - Dec 31 2011

    LINKING GENETIC PROGRAMS OF DIVERSITY TO ES CELL MOTOR NEURO N CONNECTIVITY (Private)

    Sep 1 2008 - Aug 31 2011

    GENETIC AND PHYSIOLOGICAL ANALYSIS OF CHOLINERGIC SYNAPSES O N MOTONEURONS: A SYNAPTIC STRIPPING HYPO (Private)

    Nov 1 2007 - Oct 31 2010

    MOTOR NEURON SUBTYPE DIVERSIFICATION--EMBRYONIC STEM (ES) CELL POTENTIALITY DEDUCED FROM DEVELOPMENTAL MECHANISM (Private)

    Feb 24 2005 - Dec 31 2008

Publications

  • Dasen, J., De Camilli, A., Wang, B., Tucker, P.W. and Jessell, T.M. (2008). Hox repertories for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell, 134, 304-316.
  • Chen, A.I., de Nooij, J.C. and Jessell, T.M. (2006). Graded activity of transcription factor Runx3 specifies the laminar termination pattern of sensory axons in the developing spinal cord. Neuron 49, 395-408.
  • Dasen, J.S., Tice, B.C., Brenner-Morton, S. and Jessell, T.M. (2005). A Hox regulatory network establishing motor neuron pool identity and target muscle connectivity. Cell 123, 477-491.
  • Price, S.R., De Marco Garcia, N.V. Ranscht, B. and Jessell, T.M. (2002). Regulation of motor neuron pool sorting by differential expression of type II cadherins. Cell, 109, 205-216.
  • Arber, S., Ladle, D., Lin, J., Frank, E. and Jessell, T.M. (2000). ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell, 101, 485-498.
  • Jessell, T.M. (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Reviews Genetics. 1, 20-29.

For a complete list of publications, please visit PubMed.gov