{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:33:37Z","timestamp":1790620417630,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The complement system is involved in a range of diverse developmental processes, including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. In this study, we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wild-type mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid\u2013deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development.<\/jats:p>","DOI":"10.4049\/jimmunol.1203072","type":"journal-article","created":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T13:35:33Z","timestamp":1361280933000},"page":"3493-3499","source":"Crossref","is-referenced-by-count":42,"title":["C5a Receptor Signaling Prevents Folate Deficiency\u2013Induced Neural Tube Defects in Mice"],"prefix":"10.1093","volume":"190","author":[{"given":"Kerina J","family":"Denny","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]},{"name":"School of Medicine, University of Queensland , Brisbane, Queensland 4029,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam G","family":"Coulthard","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Jeanes","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Lisgo","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University , Newcastle-upon-Tyne NE1 3BZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Simmons","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie K","family":"Callaway","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Queensland , Brisbane, Queensland 4029,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Dell Pediatric Research Institute, University of Texas , Austin, TX 78723"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H","family":"Finnell","sequence":"additional","affiliation":[{"name":"Dell Pediatric Research Institute, University of Texas , Austin, TX 78723"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent M","family":"Woodruff","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Taylor","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Queensland , Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406465955200_r1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s00251-006-0142-1","article-title":"Genomic view of the evolution of the complement system","volume":"58","author":"Nonaka","year":"2006","journal-title":"Immunogenetics"},{"key":"2025032406465955200_r2","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1084\/jem.20030374","article-title":"The proinflammatory mediators C3a and C5a are essential for liver regeneration","volume":"198","author":"Strey","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025032406465955200_r3","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1385\/IR:27:2-3:367","article-title":"Complement: structure, functions, evolution, and viral molecular mimicry","volume":"27","author":"Mastellos","year":"2003","journal-title":"Immunol. Res."},{"key":"2025032406465955200_r4","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1182\/blood-2002-10-3233","article-title":"Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem\/progenitor cells, and C3a enhances their homing-related responses to SDF-1","volume":"101","author":"Reca","year":"2003","journal-title":"Blood"},{"key":"2025032406465955200_r5","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1096\/fj.11-202382","article-title":"Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis","volume":"26","author":"Pavlovski","year":"2012","journal-title":"FASEB J."},{"key":"2025032406465955200_r6","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1387\/ijdb.072465v","article-title":"Expression of complement components coincides with early patterning and organogenesis in Xenopus laevis","volume":"52","author":"McLin","year":"2008","journal-title":"Int. J. Dev. Biol."},{"key":"2025032406465955200_r7","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nrn1986","article-title":"Neural tube defects and folate: case far from closed","volume":"7","author":"Blom","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"2025032406465955200_r8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/tera.1420340206","article-title":"Neural tube defects: a review of human and animal studies on the etiology of neural tube defects","volume":"34","author":"Campbell","year":"1986","journal-title":"Teratology"},{"key":"2025032406465955200_r9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1749-6632.2000.tb06886.x","article-title":"Genetic basis of susceptibility to environmentally induced neural tube defects","volume":"919","author":"Finnell","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025032406465955200_r10","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1136\/adc.51.12.944","article-title":"Vitamin deficiencies and neural tube defects","volume":"51","author":"Smithells","year":"1976","journal-title":"Arch. Dis. Child."},{"key":"2025032406465955200_r11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/tera.10040","article-title":"Investigation of the effects of folate deficiency on embryonic development through the establishment of a folate deficient mouse model","volume":"65","author":"Burgoon","year":"2002","journal-title":"Teratology"},{"key":"2025032406465955200_r12","first-page":"101","article-title":"Coprophagy in female mice during pregnancy and lactation","volume":"37","author":"Ebino","year":"1988","journal-title":"Jikken Dobutsu"},{"key":"2025032406465955200_r13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0925-4773(95)00383-5","article-title":"Murine Wnt-11 and Wnt-12 have temporally and spatially restricted expression patterns during embryonic development","volume":"51","author":"Christiansen","year":"1995","journal-title":"Mech. Dev."},{"key":"2025032406465955200_r14","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.4049\/jimmunol.165.10.5406","article-title":"Cutting edge: targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock","volume":"165","author":"Kildsgaard","year":"2000","journal-title":"J. Immunol."},{"key":"2025032406465955200_r15","doi-asserted-by":"crossref","first-page":"6560","DOI":"10.4049\/jimmunol.164.12.6560","article-title":"A new small molecule C5a receptor antagonist inhibits the reverse-passive Arthus reaction and endotoxic shock in rats","volume":"164","author":"Strachan","year":"2000","journal-title":"J. Immunol."},{"key":"2025032406465955200_r16","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.molimm.2011.04.014","article-title":"Inhibiting the C5-C5a receptor axis","volume":"48","author":"Woodruff","year":"2011","journal-title":"Mol. Immunol."},{"key":"2025032406465955200_r17","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.devcel.2011.10.012","article-title":"Complement fragment C3a controls mutual cell attraction during collective cell migration","volume":"21","author":"Carmona-Fontaine","year":"2011","journal-title":"Dev. Cell"},{"key":"2025032406465955200_r18","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The classical complement cascade mediates CNS synapse elimination","volume":"131","author":"Stevens","year":"2007","journal-title":"Cell"},{"key":"2025032406465955200_r19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1399-0004.2009.01174.x","article-title":"Importance of gene-environment interactions in the etiology of selected birth defects","volume":"75","author":"Zhu","year":"2009","journal-title":"Clin. Genet."},{"issue":"Suppl. 2","key":"2025032406465955200_r20","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1177\/15648265080292S112","article-title":"Gene-nutrient interactions: importance of folic acid and vitamin B12 during early embryogenesis","volume":"29","author":"Finnell","year":"2008","journal-title":"Food Nutr. Bull."},{"key":"2025032406465955200_r21","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1084\/jem.20061022","article-title":"Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction","volume":"203","author":"Girardi","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032406465955200_r22","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S0140-6736(97)01342-1","article-title":"Can terathanasia explain the protective effect of folic-acid supplementation on birth defects?","volume":"350","author":"Hook","year":"1997","journal-title":"Lancet"},{"key":"2025032406465955200_r23","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1016\/j.biocel.2007.06.012","article-title":"Differentially expressed genes implicated in unexplained recurrent spontaneous abortion","volume":"39","author":"Lee","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2025032406465955200_r24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0140-6736(91)90133-A","article-title":"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study","volume":"338","author":"MRC Vitamin Study Research Group","year":"1991","journal-title":"Lancet"},{"key":"2025032406465955200_r25","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0002-9378(94)70224-1","article-title":"Are obese women at higher risk for producing malformed offspring?","volume":"170","author":"Waller","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2025032406465955200_r26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/ajmg.c.30051","article-title":"Mouse models of neural tube defects: investigating preventive mechanisms","volume":"135C","author":"Greene","year":"2005","journal-title":"Am. J. Med. Genet. C. Semin. Med. Genet."},{"key":"2025032406465955200_r27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ng0796-275","article-title":"Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene","volume":"13","author":"Zhao","year":"1996","journal-title":"Nat. Genet."},{"key":"2025032406465955200_r28","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1126\/science.280.5372.2107","article-title":"Embryonic folate metabolism and mouse neural tube defects","volume":"280","author":"Fleming","year":"1998","journal-title":"Science"},{"key":"2025032406465955200_r29","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/hmg\/11.3.283","article-title":"Folic acid prevents exencephaly in Cited2 deficient mice","volume":"11","author":"Barbera","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2025032406465955200_r30","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/hmg\/9.6.993","article-title":"Mouse models for neural tube closure defects","volume":"9","author":"Juriloff","year":"2000","journal-title":"Hum. Mol. Genet."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/7\/3493\/62503254\/1203072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/7\/3493\/62503254\/1203072.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T04:33:57Z","timestamp":1742963637000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/190\/7\/3493\/8004113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,1]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1203072","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,4]]},"published":{"date-parts":[[2013,4,1]]}}}