Dr. Wichterle's lab utilizes in vitro differentiation of embryonic stem cells as a proxy to study development of mammalian nervous system. They have developed robust protocols for directed differentiation of mouse ES cells into distinct subsets of skeletal and autonomic motor neurons. ES cell-derived motor neurons acquire appropriate electrophysiological properties and innervate muscle targets upon transplantation into the developing neural tube. Utilizing the in vitro system they aim to define genetic programs controlling conversion of pluripotent stem cells to distinct subtypes of spinal motor neurons. In addition, they are developing ES cell-based models of motor neuron diseases to study motor neuron survival, axon pathfinding and synapse formation in normal and diseased cells to define pathologic processes initiating motor neuron degeneration and to develop cell based system for drug discovery.
Jun-An Chen, Yuan-Ping Huang, Esteban O. Mazzoni, G. Christopher Tan, Jiri Zavadil, and Hynek Wichterle.
Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-repressive Loop. Neuron 69(4):721-35. (2011)
Shi, P., Nedelec, S., Wichterle, H., and Kam, L.C.
Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding. Lab Chip 10:1005-10. (2010)
Jung, H., Lacombe, J., Mazzoni, E.O., Liem, K.F., Jr., Grinstein, J., Mahony, S., Mukhopadhyay, D., Gifford, D.K., Young, R.A., Anderson, K.V., Wichterle, H., and Dasen, J.S.
Global control of motor neuron topography mediated by the repressive actions of a single hox gene. Neuron 67:781-96. (2010)
Peljto, M., Dasen, J.S., Mazzoni, E.O., Jessell, T.M., and Wichterle, H.
Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell 7:355-366. (2010)
Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., Wichterle, H., Henderson, C.E., and Eggan, K.,
Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218-21. (2008)