Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development
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) l...
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2023-10-01
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author | Tamás Kovács Viktória Halasy Csongor Pethő Emőke Szőcs Ádám Soós Dávid Dóra Pascal de Santa Barbara Sandrine Faure Rhian Stavely Allan M. Goldstein Nándor Nagy |
author_facet | Tamás Kovács Viktória Halasy Csongor Pethő Emőke Szőcs Ádám Soós Dávid Dóra Pascal de Santa Barbara Sandrine Faure Rhian Stavely Allan M. Goldstein Nándor Nagy |
author_sort | Tamás Kovács |
collection | DOAJ |
description | 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. |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T11:28:46Z |
publishDate | 2023-10-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-7acb4ea42b0049b380d203aec042052e2023-11-10T15:04:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124211566410.3390/ijms242115664Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System DevelopmentTamás Kovács0Viktória Halasy1Csongor Pethő2Emőke Szőcs3Ádám Soós4Dávid Dóra5Pascal de Santa Barbara6Sandrine Faure7Rhian Stavely8Allan M. Goldstein9Nándor Nagy10Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryPhyMedExp, University of Montpellier, INSERM, CNRS, 34295 Montpellier, FrancePhyMedExp, University of Montpellier, INSERM, CNRS, 34295 Montpellier, FrancePediatric Surgery Research Laboratories, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAPediatric Surgery Research Laboratories, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADepartment of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 1094 Budapest, HungaryThe 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.https://www.mdpi.com/1422-0067/24/21/15664enteric nervous systemneural crestcecahindgutHirschsprung diseaseBMP4 |
spellingShingle | Tamás Kovács Viktória Halasy Csongor Pethő Emőke Szőcs Ádám Soós Dávid Dóra Pascal de Santa Barbara Sandrine Faure Rhian Stavely Allan M. Goldstein Nándor Nagy Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development International Journal of Molecular Sciences enteric nervous system neural crest ceca hindgut Hirschsprung disease BMP4 |
title | Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development |
title_full | Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development |
title_fullStr | Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development |
title_full_unstemmed | Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development |
title_short | Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development |
title_sort | essential role of bmp4 signaling in the avian ceca in colorectal enteric nervous system development |
topic | enteric nervous system neural crest ceca hindgut Hirschsprung disease BMP4 |
url | https://www.mdpi.com/1422-0067/24/21/15664 |
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