Directed differentiation of embryonic stem cells into motor neurons.
Inductive signals and transcription factors involved in motor neuron generation have been identified, raising the question of whether these developmental insights can be used to direct stem cells to a motor neuron fate. We show that developmentally relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo. ES cell-derived motor neurons can populate the embryonic spinal cord, extend axons, and form synapses with target muscles. Thus, inductive signals involved in normal pathways of neurogenesis can direct ES cells to form specific classes of CNS neurons.
Wichterle
Hynek
H
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Lieberam
Ivo
I
Porter
Jeffery A
JA
Jessell
Thomas M
TM
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004627:Embryonic Induction / Q000187:drug effects / Q000502:physiology*; D006085:Graft Survival / Q000502:physiology; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000819:agonists / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C084059:Hb9 protein, mouse; D049452:Green Fluorescent Proteins; D014212:Tretinoin