Hynek Wichterle, PhD
- Co-Director, Motor Neuron Center
My laboratory models and studies the development of the nervous system in a culture dish. We have pioneered some of the most efficient methods for the differentiation of pluripotent embryonic stem cells into specific subtypes of spinal motor neurons and interneurons in vitro. The process faithfully recapitulates normal embryonic development, providing a unique opportunity to study neural development at a biochemical level in a controlled environment outside of the embryo.
We combine the differentiation system with CRISPR based genome editing and with inducible transgene expression to decode transcriptional programs controlling progressive transitions from a pluripotent stem cell to a defined postmitotic neuron. We assembled a global map of genomic regulatory elements controlling motor neuron expression program. Our ultimate goal is to decipher the syntax and grammar of the "language" used by transcription factors to specify neuronal cell identity during embryonic development.
The lab also capitalizes on the unlimited source of spinal neurons to study molecular processes underlying neuronal maturation, synapse formation, and neuronal aging and degeneration. We are using both mouse and human pluripotent stem cells to model motor neuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), with the goal of discovering new drugs that promote motor neuron survival.
“Cell Specification & Differentiation; Neural Degeneration & Repair; Stem Cell Biology“
Rhee, H.S., Closser, M., Guo, Y., Bashkirova, E.V., Tan, G.C., Gifford, D.K., and Wichterle, H. (2016). Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers. Neuron 92, 1252-1265.
Tan GC, Mazzoni EO, Wichterle H. Iterative Role of Notch Signaling in Spinal Motor Neuron Diversification. Cell Rep. 2016 Jul 26;16(4):907-16.
Mazzoni, E.O., Mahony, S., Closser, M., Morrison, C.A., Nedelec, S., Williams, D.J., An, D., Gifford, D.K., and Wichterle, H. (2013a). Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity. Nature neuroscience 16, 1219-1227.
Mazzoni, E.O., Mahony, S., Peljto, M., Patel, T., Thornton, S.R., McCuine, S., Reeder, C., Boyer, L.A., Young, R.A., Gifford, D.K., and Wichterle, H. (2013b). Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals. Nature neuroscience 16, 1191-1198.
Amoroso, M.W., Croft, G.F., Williams, D.J., O'Keeffe, S., Carrasco, M.A., Davis, A.R., Roybon, L., Oakley, D.H., Maniatis, T., Henderson, C.E., and Wichterle, H. (2013). Accelerated High-Yield Generation of Limb-Innervating Motor Neurons from Human Stem Cells. J Neurosci 33, 574-586.
Nedelec, S., Peljto, M., Shi, P., Amaroso, M., Kam, L, and Wichterle, H. Concentration dependent requirement for local protein synthesis in motor neuron subtype specific response to axon guidance cues. J Neurosci. 2012;32(4):1496-506.
Chen, J. A., Huang, Y. P., Mazzoni, E. O., Tan, G. C., Zavadil, J., Wichterle, H., 2011. Mir-17-3p controls spinal neural progenitor patterning by regulating olig2/irx3 cross-repressive loop. Neuron. 69, 721-35.
Peljto, M., Dasen, J.S., Mazzoni, E.O., Jessell, T.M., and Wichterle, H. (2010). Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell 7, 355-366.
Wichterle, H., Lieberam, I., Porter, J. A., and Jessell, T. M. (2002). Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385-397.
For a complete list of publications, please visit PubMed.gov