title: 3D reconstitution of the patterned neural tube from embryonic stem cells.
abstract: Inducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill defined, as embryoid bodies typically contained many cell types. Here we show that single mouse ESCs directly embedded in Matrigel or defined synthetic matrices under neural induction conditions can clonally form neuroepithelial cysts containing a single lumen in 3D. Untreated cysts were uniformly dorsal and could be ventralized to floor plate (FP). Retinoic acid posteriorized cysts to cervical levels and induced localize FP formation yielding full patterning along the dorsal/ventral (DV) axis. Correct spatial organization of motor neurons, interneurons, and dorsal interneurons along the DV axis was observed. This system serves as a valuable tool for studying morphogen action in 3D and as a source of patterned spinal cord tissue.
authors.affiliation: DFG-Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Meinhardt
authors.affiliation: DFG-Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Eberle
authors.affiliation: DFG-Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Akira
authors.initials: A
authors.lastname: Tazaki
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ranga
authors.affiliation: Neurosurgery Department, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Niesche
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wilsch-Bräuninger
authors.affiliation: DFG-Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Stec
authors.affiliation: Neurosurgery Department, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lutolf
authors.affiliation: DFG-Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: elly.tanaka@crt-dresden.de.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D015415:Biomarkers; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics; D051379:Mice; D054259:Neural Tube / Q000166:cytology* / Q000502:physiology*; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics; D046509:Tissue Culture Techniques; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D053823:Hedgehog Proteins; D014212:Tretinoin