{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:36:07Z","timestamp":1768314967134,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In mice, Schwann cell (SC) progenitors give rise to autonomic ganglion cells and migrate into the gut to become enteric neurons. It is unknown whether SC progenitors have a similar fate in humans. In search of evidence for human SC\u2010derived neurogenesis in the gastrointestinal (GI) tract, we studied the rectums from cadaveric controls and children with anorectal malformations (ARM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed distal rectal tissue taken at autopsy from 10 children with normal GI tracts and resected rectal specimens in 48 cases of ARM. Of these specimens, 6 had neurons within the extrinsic rectal innervation. These were further investigated with immunohistochemistry for neuronal and SC\/glial markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Perirectal tissue from control and ARM contained GLUT1\u2010positive extrinsic nerves, many containing neurons. SC\/glial markers (SOX10, CDH19, and PLP1) were expressed by glia in the enteric nervous system and perirectal nerves, while MPZ predominated only in glia of perirectal nerves, in both control and ARM. Neurons in perirectal nerves were 61% larger in ARM samples and co\u2010expressed SOX10 (81%), PLP1 (73%), and CDH19 (56%). In ARM, cytoplasmic SOX10 was co\u2010expressed with neuronal antigens in ~57% of submucosal and myenteric neurons, vs. ~3% in control. Furthermore, intrinsic gut neurons in ARM specimens co\u2010expressed PLP1 (18%) and CDH19 (18%); however, neuronal co\u2010expression of PLP1 and CDH19 was rarely (&lt;2%) observed in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Dual expression of glial and neuronal markers in rectal and perirectal neurons support a model of Schwann cell\u2010derived neurogenesis in the innervation of the human GI tract.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14074","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T12:11:06Z","timestamp":1609416666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neurons populating the rectal extrinsic nerves in humans express neuronal and Schwann cell markers"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-6215","authenticated-orcid":false,"given":"Crystal","family":"Woods","sequence":"first","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition Department of Pediatrics University of Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj P.","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Pathology Seattle Children's Hospital and University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery International Center for Colorectal and Urogenital Care Children's Hospital Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Pathology Children\u2019s Hospital Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Pathology Children\u2019s Hospital Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery International Center for Colorectal and Urogenital Care Children's Hospital Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Flockton","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition Department of Pediatrics University of Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology Hotchkiss Brain Institute Cumming School of Medicine University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3733-2127","authenticated-orcid":false,"given":"Jaime","family":"Belkind\u2010Gerson","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition Department of Pediatrics University of Colorado Aurora CO USA"},{"name":"Neurogastroenterology and Motility Program Digestive Health Institute Children\u2019s Hospital Colorado Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0271-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.107"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.32"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.09.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253286"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.01.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1239-15.2015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.19-0173"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.186619"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00164.2014"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12015"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02890-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20592"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1093526617697060"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63401"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20748"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22876"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490260202"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20209"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.5858\/2000-124-1314-SDOMNI"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.41.12.1587"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1093526618817658"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1093526619889436"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(90)90394-O"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294605"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0568-3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199910)216:2<137::AID-DVDY5>3.0.CO;2-6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.149815"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92707-7"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22746"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.186619"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1072217"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58200"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10721"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58186"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619406114"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000326"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.150656"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.16.5826-5834.2002"}],"container-title":["Neurogastroenterology &amp; 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