{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:22:00Z","timestamp":1777933320904,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T00:00:00Z","timestamp":1303776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>\n                    Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model,\n                    <jats:italic toggle=\"yes\">Splotch<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ), which has a homozygous loss-of-function mutation in the\n                    <jats:italic toggle=\"yes\">Pax3<\/jats:italic>\n                    gene. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (\n                    <jats:italic toggle=\"yes\">WT<\/jats:italic>\n                    ) and\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    embryos compared with\n                    <jats:italic toggle=\"yes\">WT<\/jats:italic>\n                    was minimal (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.05). Addition of FA to\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cultures increased the expression of a Pax3 downstream target,\n                    <jats:italic toggle=\"yes\">fgfr4<\/jats:italic>\n                    , and rescued NSC proliferative potential, as demonstrated by a significant increase in neurosphere formation (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01). To ascertain if FA affected cell differentiation, FA-stimulated\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as\n                    <jats:italic toggle=\"yes\">WT<\/jats:italic>\n                    . Further, multiple neurospheres from both\n                    <jats:italic toggle=\"yes\">WT<\/jats:italic>\n                    and FA-stimulated\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated\n                    <jats:italic toggle=\"yes\">Sp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    neurospheres differentiate and form synaptic connections, comparable to\n                    <jats:italic toggle=\"yes\">WT<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1089\/scd.2011.0100","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T12:19:36Z","timestamp":1303820376000},"page":"321-330","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["Fetal Neural Tube Stem Cells from\n                    <i>Pax3<\/i>\n                    Mutant Mice Proliferate, Differentiate, and Form Synaptic Connections When Stimulated with Folic Acid"],"prefix":"10.1177","volume":"21","author":[{"given":"Shunsuke","family":"Ichi","sequence":"first","affiliation":[{"name":"Northwestern University"},{"name":"University of Tokyo","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Nakazaki","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanda","family":"Boshnjaku","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravneet Monny","family":"Singh","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Mania-Farnell","sequence":"additional","affiliation":[{"name":"Purdue University at Calumet"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guifa","family":"Xi","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"McLone","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadanori","family":"Tomita","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra Shekhar K.","family":"Mayanil","sequence":"additional","affiliation":[{"name":"Northwestern University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,4,26]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00009"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067103"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5372.2107"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.09.008"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.54.353"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn262"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20333"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.532"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10019"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.01.008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990601)56:5<518::AID-JNR7>3.0.CO;2-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00098-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","unstructured":"Pacey LK Stead S Gleave JA Tomczyk K Doering LC. 2006. 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