Nature Biotechnology
23, 215 - 221 (2005)
Published online: 30 January 2005; | doi:10.1038/nbt1063
Specification of motoneurons from human embryonic stem cellsXue-Jun Li1, 2, 4, Zhong-Wei Du1, 2, 4, Ewa D Zarnowska3, Matthew Pankratz4, Lauren O Hansen4, Robert A Pearce3
& Su-Chun Zhang1, 2, 41
Department of Anatomy, Waisman Center, 1500 Highland Avenue, University of Wisconsin-Madison, Wisconsin 53705, USA. 2
Department of Neurology, Waisman Center, 1500 Highland Avenue, University of Wisconsin-Madison, Wisconsin 53705, USA. 3
Department of Anesthesiology, School of Medicine, Waisman Center, 1500 Highland Avenue, University of Wisconsin-Madison, Wisconsin 53705, USA. 4
the Stem Cell Research Program, Waisman Center, 1500 Highland Avenue, University of Wisconsin-Madison, Wisconsin 53705, USA.
Correspondence should be addressed to Su-Chun Zhang zhang@waisman.wisc.eduAn understanding of how mammalian stem cells produce specific neuronal subtypes remains elusive. Here we show that human embryonic stem cells generated early neuroectodermal cells, which organized into rosettes and expressed Pax6 but not Sox1, and then late neuroectodermal cells, which formed neural tube−like structures and expressed both Pax6 and Sox1. Only the early, but not the late, neuroectodermal cells were efficiently posteriorized by retinoic acid and, in the presence of sonic hedgehog, differentiated into spinal motoneurons. The in vitro−generated motoneurons expressed HB9, HoxC8, choline acetyltransferase and vesicular acetylcholine transporter, induced clustering of acetylcholine receptors in myotubes, and were electrophysiologically active. These findings indicate that retinoic acid action is required during neuroectoderm induction for motoneuron specification and suggest that stem cells have restricted capacity to generate region-specific projection neurons even at an early developmental stage.
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