References
Brookhart, J. M. (1952). A study of corticospinal activation of motor neurons. Research Publications—Association for Research in Nervous and Mental Disease, 30, 157–173.
Dupuis, L., Gonzalez de Aguilar, J. L., Echaniz-Laguna, A., Eschbach, J., Rene, F., Oudart, H., et al. (2009). Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons. PLoS One, 4(4), e5390. doi:10.1371/journal.pone.0005390.
Dupuis, L., & Loeffler, J. P. (2009). Neuromuscular junction destruction during amyotrophic lateral sclerosis: Insights from transgenic models. Current Opinion in Pharmacology, 9(3), 341–346. doi:10.1016/j.coph.2009.03.007.
Hamburger, V. (1975). Cell death in the development of the lateral motor column of the chick embryo. The Journal of Comparative Neurology, 160(4), 535–546. doi:10.1002/cne.901600408.
Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.
Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., et al. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473(7346), 221–225. doi:10.1038/nature09915.
Walsh, R. M., & Hochedlinger, K. (2010). Modeling Rett syndrome with stem cells. Cell, 143(4), 499–500. doi:10.1016/j.cell.2010.10.037.
Grabrucker, A., Vaida, B., Bockmann, J., & Boeckers, T. M. (2009). Synaptogenesis of hippocampal neurons in primary cell culture. Cell and Tissue Research, 338(3), 333–341. doi:10.1007/s00441-009-0881-z.
Kawaguchi, A., Ikawa, T., Kasukawa, T., Ueda, H. R., Kurimoto, K., Saitou, M., et al. (2008). Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development, 135(18), 3113–3124. doi:10.1242/dev.022616.
Liebau, S., Vaida, B., Storch, A., & Boeckers, T. M. (2007). Maturation of synaptic contacts in differentiating neural stem cells. Stem Cells, 25(7), 1720–1729.
Walther, P., Wang, L., Liessem, S., & Frascaroli, G. (2010). Viral infection of cells in culture–approaches for electron microscopy. Methods in Cell Biology, 96, 603–618. doi:10.1016/S0091-679X(10)96025-1.
Baron, M. K., Boeckers, T. M., Vaida, B., Faham, S., Gingery, M., Sawaya, M. R., et al. (2006). An architectural framework that may lie at the core of the postsynaptic density. Science, 311(5760), 531–535. doi:10.1126/science.1118995.
Dale, H. H., Feldberg, W., & Vogt, M. (1936). Release of acetylcholine at voluntary motor nerve endings. The Journal of Physiology, 86(4), 353–380.
Wu, H., Xiong, W. C., & Mei, L. (2010). To build a synapse: Signaling pathways in neuromuscular junction assembly. Development, 137(7), 1017–1033. doi:10.1242/dev.038711.
Sanes, J. R., Marshall, L. M., & McMahan, U. J. (1978). Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. Journal of Cell Biology, 78(1), 176–198.
Witzemann, V. (2006). Development of the neuromuscular junction. Cell and Tissue Research, 326(2), 263–271. doi:10.1007/s00441-006-0237-x.
Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26(11), 1276–1284. doi:10.1038/nbt.1503.
Linta, L., Stockmann, M. C., Kleinhans, K. N., Boeckers, A., Storch, A., Zaehres, H., et al. (2011). Rat embryonic fibroblasts improve reprogramming of human keratinocytes into induced pluripotent stem cells. Stem Cells and Development. doi:10.1089/scd.2011.0026.
Hu, B. Y., & Zhang, S. C. (2009). Differentiation of spinal motor neurons from pluripotent human stem cells. Nature Protocols, 4(9), 1295–1304. doi:10.1038/nprot.2009.127.
Bischoff, R., & Heintz, C. (1994). Enhancement of skeletal muscle regeneration. Developmental Dynamics, 201(1), 41–54.
Kleger, A., Seufferlein, T., Malan, D., Tischendorf, M., Storch, A., Wolheim, A., et al. (2010). Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. Circulation, 122(18), 1823–1836. doi:10.1161/CIRCULATIONAHA.110.971721.
Liebau, S., Steinestel, J., Linta, L., Kleger, A., Storch, A., Schoen, M., et al. (2011). An SK3 Channel/nWASP/Abi-1 complex is involved in early neurogenesis. PLoS One, 6(3), e18148. doi:10.1371/journal.pone.0018148.
Liebau, S., Vaida, B., Proepper, C., Grissmer, S., Storch, A., Boeckers, T. M., et al. (2007). Formation of cellular projections in neural progenitor cells depends on SK3 channel activity. Journal of Neurochemistry, 101(5), 1338–1350. doi:10.1111/j.1471-4159.2006.04437.x.
Ludolph, A. G., Udvardi, P. T., Schaz, U., Henes, C., Adolph, O., Weigt, H. U., et al. (2010). Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. British Journal of Pharmacology, 160(2), 283–291. doi:10.1111/j.1476-5381.2010.00707.x.
Li, X. J., Du, Z. W., Zarnowska, E. D., Pankratz, M., Hansen, L. O., Pearce, R. A., et al. (2005). Specification of motoneurons from human embryonic stem cells. Nature Biotechnology, 23(2), 215–221. doi:10.1038/nbt1063.
Somers, A., Jean, J. C., Sommer, C. A., Omari, A., Ford, C. C., Mills, J. A., et al. (2010). Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells, 28(10), 1728–1740. doi:10.1002/stem.495.
de Castro, B. M., De Jaeger, X., Martins-Silva, C., Lima, R. D., Amaral, E., Menezes, C., et al. (2009). The vesicular acetylcholine transporter is required for neuromuscular development and function. Molecular and Cellular Biology, 29(19), 5238–5250. doi:10.1128/MCB.00245-09.
Weihe, E., Tao-Cheng, J. H., Schafer, M. K., Erickson, J. D., & Eiden, L. E. (1996). Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America, 93(8), 3547–3552.
Zhang, H., Wu, C. Y., Wang, W., & Harrington, M. A. (2011). Interneuronal synapses formed by motor neurons appear to be glutamatergic. Neuroreport, 22(16), 809–813. doi:10.1097/WNR.0b013e32834b6d5c.
Sanchez-Ponce, D., Tapia, M., Munoz, A., & Garrido, J. J. (2008). New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and axon initial segment development. Molecular and Cellular Neuroscience, 37(4), 832–844. doi:10.1016/j.mcn.2008.01.010.
Garner, C. C., Waites, C. L., & Ziv, N. E. (2006). Synapse development: Still looking for the forest, still lost in the trees. Cell and Tissue Research, 326(2), 249–262. doi:10.1007/s00441-006-0278-1.
Hayashi, M. K., Tang, C., Verpelli, C., Narayanan, R., Stearns, M. H., Xu, R. M., et al. (2009). The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell, 137(1), 159–171. doi:10.1016/j.cell.2009.01.050.
Boeckers, T. M. (2006). The postsynaptic density. Cell and Tissue Research, 326(2), 409–422. doi:10.1007/s00441-006-0274-5.
Han, K., & Kim, E. (2008). Synaptic adhesion molecules and PSD-95. Progress in Neurobiology, 84(3), 263–283. doi:10.1016/j.pneurobio.2007.10.011.
Grabrucker, A. M., Knight, M. J., Proepper, C., Bockmann, J., Joubert, M., Rowan, M., et al. (2011). Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. The EMBO Journal, 30(3), 569–581. doi:10.1038/emboj.2010.336.
Song, J. Y., Ichtchenko, K., Sudhof, T. C., & Brose, N. (1999). Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proceedings of the National Academy of Sciences of the United States of America, 96(3), 1100–1105.
Blasi, J., Chapman, E. R., Link, E., Binz, T., Yamasaki, S., De Camilli, P., et al. (1993). Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature, 365(6442), 160–163. doi:10.1038/365160a0.
Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., et al. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4335–4340. doi:10.1073/pnas.0910012107.
Ko, J. Y., Park, C. H., Koh, H. C., Cho, Y. H., Kyhm, J. H., Kim, Y. S., et al. (2007). Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. Journal of Neurochemistry, 103(4), 1417–1429. doi:10.1111/j.1471-4159.2007.04898.x.
Liu, G. H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S. L., et al. (2011). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature, 472(7342), 221–225. doi:10.1038/nature09879.
Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., et al. (2011). Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471(7337), 225–229. doi:10.1038/nature09747.
Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893), 1218–1221. doi:10.1126/science.1158799.
Inoue, H. (2010). Neurodegenerative disease-specific induced pluripotent stem cell research. Experimental Cell Research, 316(16), 2560–2564. doi:10.1016/j.yexcr.2010.04.022.
Boulting, G. L., Kiskinis, E., Croft, G. F., Amoroso, M. W., Oakley, D. H., Wainger, B. J., et al. (2011). A functionally characterized test set of human induced pluripotent stem cells. Nature Biotechnology. doi:10.1038/nbt.1783.
Kim, J. E., O’Sullivan, M. L., Sanchez, C. A., Hwang, M., Israel, M. A., Brennand, K., et al. (2011). Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3005–3010. doi:10.1073/pnas.1007753108.
Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. M. (2002). Directed differentiation of embryonic stem cells into motor neurons. Cell, 110(3), 385–397.
Acknowledgements
The authors would like to thank Sabine Seltenheim for excellent technical support, the central electron microscopy unit of Ulm University for help with embedding and electron microscopy setups, Frank Edenhofer (Bonn, Germany) for providing recombinant Cre protein and Gustavo Mostoslavsky for providing the reprogramming vector construct. This study was supported by the Deutsche Forschungsgemeinschaft (SFB497/B8 to TMB and DFG BO1718/4-1 to StL and TMB).
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Marianne Stockmann and Leonhard Linta contributed equally
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Stockmann, M., Linta, L., Föhr, K.J. et al. Developmental and Functional Nature of Human iPSC Derived Motoneurons. Stem Cell Rev and Rep 9, 475–492 (2013). https://doi.org/10.1007/s12015-011-9329-4
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DOI: https://doi.org/10.1007/s12015-011-9329-4