{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:06:48Z","timestamp":1790518008233,"version":"4.1.0"},"reference-count":121,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T00:00:00Z","timestamp":1451260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Resolving the mechanisms underlying human neuronal diversification remains a major challenge in developmental and applied neurobiology. Motor neurons (MNs) represent a diverse pool of neuronal subtypes exhibiting differential vulnerability in different human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). The ability to predictably manipulate MN subtype lineage restriction from human pluripotent stem cells (PSCs) will form the essential basis to establishing accurate, clinically relevant <jats:italic>in vitro<\/jats:italic> disease models. I first overview motor neuron developmental biology to provide some context for reviewing recent studies interrogating pathways that influence the generation of MN diversity. I conclude that motor neurogenesis from PSCs provides a powerful reductionist model system to gain insight into the developmental logic of MN subtype diversification and serves more broadly as a leading exemplar of potential strategies to resolve the molecular basis of neuronal subclass differentiation within the nervous system. These studies will in turn permit greater mechanistic understanding of differential MN subtype vulnerability using <jats:italic>in vitro<\/jats:italic> human disease models.<\/jats:p>","DOI":"10.1155\/2016\/1036974","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T21:01:15Z","timestamp":1451336475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Generating Diverse Spinal Motor Neuron Subtypes from Human Pluripotent Stem Cells"],"prefix":"10.1155","volume":"2016","author":[{"given":"Rickie","family":"Patani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,28]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1063"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404700101"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07677"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.235184"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn786"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn747"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(03)00015-1"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35049541"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)80028-3"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15424"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.22.5103"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)00544-x"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02051"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.019"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.008"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20080"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02478"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/10320"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20401"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.Supplement_2.105"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.11.3339"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90514-2"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/375322a0"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90397-6"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81386-0"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90276-7"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117.3.1001"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925583"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81114-9"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.8.2265"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80323-2"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.1997.062.01.053"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80853-3"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/19315"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.820400"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)00412-3"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-437x(05)80079-6"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)00413-5"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)80026-x"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80985-X"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(01)80027-1"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00172-0"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn750"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.25.112701.142916"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81591-3"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(03)00532-4"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.6.969"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01718"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903070207"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(02)00863-2"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00358"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20103"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(94)90132-5"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90387-r"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.007567"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.09.009"},{"key":"e_1_2_9_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-437x(98)80113-5"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.10.032"},{"key":"e_1_2_9_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02946"},{"key":"e_1_2_9_63_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.19.4201"},{"key":"e_1_2_9_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-133X(03)00003-6"},{"key":"e_1_2_9_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.025"},{"key":"e_1_2_9_66_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1689808"},{"key":"e_1_2_9_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(74)90090-7"},{"key":"e_1_2_9_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/336688a0"},{"key":"e_1_2_9_69_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13726"},{"key":"e_1_2_9_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/292154a0"},{"key":"e_1_2_9_71_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.012583"},{"key":"e_1_2_9_72_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.021147"},{"key":"e_1_2_9_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1001-971"},{"key":"e_1_2_9_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1102"},{"key":"e_1_2_9_75_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1145"},{"key":"e_1_2_9_76_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmsr040330"},{"key":"e_1_2_9_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.12.001"},{"key":"e_1_2_9_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm979"},{"key":"e_1_2_9_79_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.22-5-770"},{"key":"e_1_2_9_80_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02553"},{"key":"e_1_2_9_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2005.07.007"},{"key":"e_1_2_9_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1827"},{"key":"e_1_2_9_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/182064a0"},{"key":"e_1_2_9_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/380064a0"},{"key":"e_1_2_9_85_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116447"},{"key":"e_1_2_9_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05142"},{"key":"e_1_2_9_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_2_9_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09591"},{"key":"e_1_2_9_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08797"},{"key":"e_1_2_9_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10284"},{"key":"e_1_2_9_91_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0562"},{"key":"e_1_2_9_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1529"},{"key":"e_1_2_9_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1201-1129"},{"key":"e_1_2_9_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.05.004"},{"key":"e_1_2_9_95_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002122"},{"key":"e_1_2_9_96_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470151808.sc01d04s4"},{"key":"e_1_2_9_97_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0338"},{"key":"e_1_2_9_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(03)65023-8"},{"key":"e_1_2_9_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2005.08.022"},{"key":"e_1_2_9_100_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1402"},{"key":"e_1_2_9_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.10.003"},{"key":"e_1_2_9_102_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007327"},{"key":"e_1_2_9_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(02)00835-8"},{"key":"e_1_2_9_104_2","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2126-14.2015"},{"key":"e_1_2_9_105_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1216"},{"key":"e_1_2_9_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.07.013"},{"key":"e_1_2_9_107_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03831.2002"},{"key":"e_1_2_9_108_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2151"},{"key":"e_1_2_9_109_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(09)88006-X"},{"key":"e_1_2_9_110_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(00)80478-x"},{"key":"e_1_2_9_111_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3049"},{"key":"e_1_2_9_112_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2003.08.006"},{"key":"e_1_2_9_113_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.01.034"},{"key":"e_1_2_9_114_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0620"},{"key":"e_1_2_9_115_2","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0906-12.2013"},{"key":"e_1_2_9_116_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07825.x"},{"key":"e_1_2_9_117_2","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2013_59"},{"key":"e_1_2_9_118_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.135"},{"key":"e_1_2_9_119_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3467"},{"key":"e_1_2_9_120_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.07.014"},{"key":"e_1_2_9_121_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135722"}],"container-title":["Stem Cells International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2016\/1036974.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2016\/1036974.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2016\/1036974","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T02:20:40Z","timestamp":1722910840000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2016\/1036974"}},"subtitle":[],"editor":[{"given":"Joel C.","family":"Glover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,12,28]]},"references-count":121,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1155\/2016\/1036974"],"URL":"https:\/\/doi.org\/10.1155\/2016\/1036974","archive":["Portico"],"relation":{},"ISSN":["1687-966X","1687-9678"],"issn-type":[{"value":"1687-966X","type":"print"},{"value":"1687-9678","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,28]]},"assertion":[{"value":"2015-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1036974"}}