title: Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation.
abstract: Cultured ESCs can form different classes of neurons, but whether these neurons can acquire specialized subtype features typical of neurons in vivo remains unclear. We show here that mouse ESCs can be directed to form highly specific motor neuron subtypes in the absence of added factors, through a differentiation program that relies on endogenous Wnts, FGFs, and Hh-mimicking the normal program of motor neuron subtype differentiation. Molecular markers that characterize motor neuron subtypes anticipate the functional properties of these neurons in vivo: ESC-derived motor neurons grafted isochronically into chick spinal cord settle in appropriate columnar domains and select axonal trajectories with a fidelity that matches that of their in vivo generated counterparts. ESC-derived motor neurons can therefore be programmed in a predictive manner to acquire molecular and functional properties that characterize one of the many dozens of specialized motor neuron subtypes that exist in vivo.
authors.affiliation: Department of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Mirza
authors.initials: M
authors.lastname: Peljto
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Dasen
authors.forename: Esteban O
authors.initials: EO
authors.lastname: Mazzoni
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.forename: Hynek
authors.initials: H
authors.lastname: Wichterle
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D017690:Cell Transplantation; D065150:Cellular Reprogramming / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000637:transplantation*; D013116:Spinal Cord / Q000166:cytology*
references.citation: Neuron. 2001 Dec 20;32(6):997-1012
references.pmid: 11754833
references.citation: Development. 2007 Aug;134(16):2889-94
references.pmid: 17660197
references.citation: Cell. 2006 Jan 27;124(2):393-405
references.pmid: 16439212
references.citation: Stem Cells. 2007 Aug;25(8):1931-9
references.pmid: 17478583
references.citation: PLoS Biol. 2006 Jul;4(8):e252
references.pmid: 16895440
references.citation: Methods Mol Biol. 2009;482:171-83
references.pmid: 19089356
references.citation: Cell. 2005 Nov 4;123(3):477-91
references.pmid: 16269338
references.citation: Cell. 2008 Jul 25;134(2):304-16
references.pmid: 18662545
references.citation: Nature. 2008 Sep 18;455(7211):351-7
references.pmid: 18716623
references.citation: Cell. 2005 Apr 8;121(1):127-39
references.pmid: 15820684
references.citation: Neuron. 2002 Aug 29;35(5):877-92
references.pmid: 12372283
references.citation: Cell. 2000 May 26;101(5):485-98
references.pmid: 10850491
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4616-21
references.pmid: 12679522
references.citation: Dev Biol. 1995 Apr;168(2):342-57
references.pmid: 7729574
references.citation: Brain Res Rev. 2008 Aug;58(2):314-21
references.pmid: 18023878
references.citation: Mech Dev. 2001 May;103(1-2):49-59
references.pmid: 11335111
references.citation: J Neurosci. 2006 Mar 22;26(12):3256-68
references.pmid: 16554476
references.citation: Cell. 2002 Aug 9;110(3):385-97
references.pmid: 12176325
references.citation: Neuron. 2003 May 22;38(4):581-96
references.pmid: 12765610
references.citation: Annu Rev Neurosci. 2010;33:409-40
references.pmid: 20367447
references.citation: Curr Top Dev Biol. 2009;88:169-200
references.pmid: 19651305
references.citation: Nat Biotechnol. 2005 Feb;23(2):215-21
references.pmid: 15685164
references.citation: J Neurobiol. 1999 Sep 5;40(3):271-87
references.pmid: 10440729
references.citation: Cell. 1991 Apr 5;65(1):175-87
references.pmid: 1840504
references.citation: Nat Neurosci. 2005 Mar;8(3):288-96
references.pmid: 15696161
references.citation: J Morphol. 1979 Nov;162(2):275-309
references.pmid: 537102
references.citation: Cell. 1998 Dec 11;95(6):817-28
references.pmid: 9865699
references.citation: Cell. 2003 Oct 31;115(3):281-92
references.pmid: 14636556
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11796-801
references.pmid: 18697938
references.citation: Nature. 2003 Oct 30;425(6961):926-33
references.pmid: 14586461
references.citation: Nat Genet. 1999 Apr;21(4):444-8
references.pmid: 10192400
references.citation: Cell. 1998 Aug 21;94(4):503-14
references.pmid: 9727493
references.citation: Neuron. 2009 Mar 12;61(5):708-20
references.pmid: 19285468
references.citation: Brain Behav Evol. 1998;51(2):90-9
references.pmid: 9491275
references.citation: Cell. 2000 Jul 21;102(2):161-73
references.pmid: 10943837
references.citation: EMBO J. 1998 Oct 15;17(20):5896-904
references.pmid: 9774334
references.citation: J Neurosci. 2002 May 1;22(9):3831-43
references.pmid: 11978858
references.citation: Cell Stem Cell. 2008 Nov 6;3(5):519-32
references.pmid: 18983967
references.citation: Nat Rev Genet. 2000 Oct;1(1):20-9
references.pmid: 11262869
references.citation: Neuron. 1998 May;20(5):971-82
references.pmid: 9620701
references.citation: J Comp Neurol. 1995 Jun 26;357(2):272-80
references.pmid: 7665729
references.citation: Neuron. 2003 Sep 25;40(1):97-111
references.pmid: 14527436
references.citation: Neuron. 2002 Aug 29;35(5):893-905
references.pmid: 12372284