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RESEARCH THEME: Use of embryonic stem cells to study motor neuron development and function
Motor neurons convey signals from the central nervous system to the rest of the organism. They facilitate diverse set of functions such as the control of posture and movements, the maintenance of homeostasis and control of visceral functions. Effective execution of these functions relies on the specification of hundreds of distinct motor neuron subtypes during embryonic development, with each motor neuron subtype acquiring a unique position within the CNS, receiving inputs from specific subsets of neurons and projecting its axon to a defined target in the periphery.

The research in my lab focuses on the development of novel approaches to study molecular mechanisms underlying the diversity and specificity of neural connections characteristic of the motor system. To overcome the limitations of the primary neural tissue, where each motor neuron subtype is represented by a relatively small number of cells, we are taking advantage of the capacity of embryonic stem (ES) cells to differentiate into specific types of nerve cells in vitro. We have developed robust protocols for the directed differentiation of mouse ES cells into distinct subsets of skeletal and autonomic motor neurons. ES cell-derived motor neurons acquire electrophysiological properties that resemble their embryo-derived counterparts and when transplanted into the developing neural tube they can populate the embryonic spinal cord, extend axons into the periphery and form synapses with muscle targets. Currently we are studying distinct subtypes of ES-derived motor neurons, with the goal of identifying mechanisms that regulate the growth of motor axons towards their specific targets. In particular, we are examining mRNA molecules that are locally translated in the growth cones of developing motor axons. We would like to understand the targeting signals for RNA translocation, how the translation of individual mRNAs is regulated and what role local protein synthesis plays in motor axon outgrowth, guidance and synapse formation.

Understanding the diversity and function of ES cell-derived motor neurons is a first step towards the development of stem cell-based models and therapies for degenerative diseases of motor neurons (e.g. amyotrophic lateral sclerosis, spinal muscular atrophy).

BACKGROUND AND EDUCATION: Hynek Wichterle is an assistant professor holding a joint appointment in the Departments of Pathology, Neurology and the Center for Neurobiology and Behavior at Columbia University Medical center. He received his M.S. degree from Charles University in Prague and his Ph.D. degree from The Rockefeller University. He did his postdoctoral research at Columbia University, where he became Assistant Professor in 2004.


1988-93 B.S./M.S. Charles University, Prague, Czech Republic
1993-95 Research Assistant, St. Elizabeth's Hospital, Boston, MA
1995-2000 Graduate fellow, The Rockefeller University, New York, NY
2000-2004 Postdoctoral fellow, Columbia University, New York, NY
2004- Assistant professor, Columbia University, New York, NY


1999 Route28 - Summits in Neurobiology on Therapeutic Potential of Neural Stem Cells, awarded first prize for a proposal on the treatment of spinal cord injury, Port Ludlow, WA
2000 selected speaker, 114th workshop on Genetic Factors that control Cell Birth, Cell allocation and Migration in the Developing Forebrain, Instituto Juan March, Madrid, Spain
2001 recipient of the Damon Runyon Cancer Research Fund postdoctoral fellowship
2002 invited speaker, Nobel conference on "Stem cell biology", Karolinska Institute, Stockholm, Sweden
2003 invited speaker, Beckman symposium "Stem cells, Regenerative Medicine and Cancer", Stanford University, CA
2003 invited speaker, International Stem Cell Conference, Singapore

  • Novitch*, B. G., Wichterle*, H., Jessell, T. M., and Sockanathan, S. (2003). A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification. Neuron 40, 81-95. *equal contribution
  • Wichterle, H., Lieberam, I., Porter, J., and Jessell, T. (2002). Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385-397.
  • Wichterle, H., Turnbull, D. H., Nery, S., Fishell, G., and Alvarez-Buylla, A. (2001). In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128, 3759-3771.
  • Wichterle, H., Garcia-Verdugo, J. M., Herrera, D. G., and Alvarez-Buylla, A. (1999). Young neurons from medial ganglionic eminence disperse in adult and embryonic brain. Nat Neurosci 2, 461-466.
  • Wichterle, H., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1997). Direct evidence for homotypic, glia-independent neuronal migration. Neuron 18, 779-791.

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