{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:34:26Z","timestamp":1766050466828,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Science Foundation NKFI","award":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"],"award-info":[{"award-number":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"]}]},{"name":"Research Excellence Program of the Innov\u00e1ci\u00f3s\u00e9s Technol\u00f3giai Miniszt\u00e9rium in Hungary","award":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"],"award-info":[{"award-number":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"]}]},{"name":"National Institutes of Health","award":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"],"award-info":[{"award-number":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"]}]},{"name":"Bolyai Fellowship from the Magyar Tudom\u00e1nyos Akad\u00e9mia (Hungarian Academy of Sciences)","award":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"],"award-info":[{"award-number":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"]}]},{"name":"New National Excellence Programme from NKFI","award":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"],"award-info":[{"award-number":["K-124740","K-138664","TKP2021-EGA-25","R01DK103785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The enteric nervous system (ENS) is principally derived from vagal neural crest cells that migrate caudally along the entire length of the gastrointestinal tract, giving rise to neurons and glial cells in two ganglionated plexuses. Incomplete migration of enteric neural crest-derived cells (ENCDC) leads to Hirschsprung disease, a congenital disorder characterized by the absence of enteric ganglia along variable lengths of the colorectum. Our previous work strongly supported the essential role of the avian ceca, present at the junction of the midgut and hindgut, in hindgut ENS development, since ablation of the cecal buds led to incomplete ENCDC colonization of the hindgut. In situ hybridization shows bone morphogenetic protein-4 (BMP4) is highly expressed in the cecal mesenchyme, leading us to hypothesize that cecal BMP4 is required for hindgut ENS development. To test this, we modulated BMP4 activity using embryonic intestinal organ culture techniques and retroviral infection. We show that overexpression or inhibition of BMP4 in the ceca disrupts hindgut ENS development, with GDNF playing an important regulatory role. Our results suggest that these two important signaling pathways are required for normal ENCDC migration and enteric ganglion formation in the developing hindgut ENS.<\/jats:p>","DOI":"10.3390\/ijms242115664","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T09:42:52Z","timestamp":1698399772000},"page":"15664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-4545","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikt\u00f3ria","family":"Halasy","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csongor","family":"Peth\u0151","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Em\u0151ke","family":"Sz\u0151cs","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1d\u00e1m","family":"So\u00f3s","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e1vid","family":"D\u00f3ra","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-2481","authenticated-orcid":false,"given":"Pascal","family":"de Santa Barbara","sequence":"additional","affiliation":[{"name":"PhyMedExp, University of Montpellier, INSERM, CNRS, 34295 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Faure","sequence":"additional","affiliation":[{"name":"PhyMedExp, University of Montpellier, INSERM, CNRS, 34295 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-3704","authenticated-orcid":false,"given":"Rhian","family":"Stavely","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Research Laboratories, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan M.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Research Laboratories, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-5214","authenticated-orcid":false,"given":"N\u00e1ndor","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/cne.901010212","article-title":"The Origin of Intrinsic Ganglia of Trunk Viscera from Vagal Neural Crest in the Chick Embryo","volume":"101","author":"Yntema","year":"1954","journal-title":"J. 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