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ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease

Hirschsprung disease (HSCR) is a neurocristopathy characterized by intestinal aganglionosis which is attributed to a failure in neural crest cell (NCC) development during the embryonic stage. The colonization of the intestine by NCCs is a process finely controlled by a wide and complex gene regulato...

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Autores principales: Villalba-Benito, Leticia, Torroglosa, Ana, Luzón-Toro, Berta, Fernández, Raquel María, Moya-Jiménez, María José, Antiñolo, Guillermo, Borrego, Salud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730166/
https://www.ncbi.nlm.nih.gov/pubmed/33260622
http://dx.doi.org/10.3390/ijms21239061
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author Villalba-Benito, Leticia
Torroglosa, Ana
Luzón-Toro, Berta
Fernández, Raquel María
Moya-Jiménez, María José
Antiñolo, Guillermo
Borrego, Salud
author_facet Villalba-Benito, Leticia
Torroglosa, Ana
Luzón-Toro, Berta
Fernández, Raquel María
Moya-Jiménez, María José
Antiñolo, Guillermo
Borrego, Salud
author_sort Villalba-Benito, Leticia
collection PubMed
description Hirschsprung disease (HSCR) is a neurocristopathy characterized by intestinal aganglionosis which is attributed to a failure in neural crest cell (NCC) development during the embryonic stage. The colonization of the intestine by NCCs is a process finely controlled by a wide and complex gene regulatory system. Several genes have been associated with HSCR, but many aspects still remain poorly understood. The present study is focused on deciphering the PAX6 interaction network during enteric nervous system (ENS) formation. A combined experimental and computational approach was performed to identify PAX6 direct targets, as well as gene networks shared among such targets as potential susceptibility factors for HSCR. As a result, genes related to PAX6 either directly (RABGGTB and BRD3) or indirectly (TGFB1, HRAS, and GRB2) were identified as putative genes associated with HSCR. Interestingly, GRB2 is involved in the RET/GDNF/GFRA1 signaling pathway, one of the main pathways implicated in the disease. Our findings represent a new contribution to advance in the knowledge of the genetic basis of HSCR. The investigation of the role of these genes could help to elucidate their implication in HSCR onset.
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spelling pubmed-77301662020-12-12 ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease Villalba-Benito, Leticia Torroglosa, Ana Luzón-Toro, Berta Fernández, Raquel María Moya-Jiménez, María José Antiñolo, Guillermo Borrego, Salud Int J Mol Sci Article Hirschsprung disease (HSCR) is a neurocristopathy characterized by intestinal aganglionosis which is attributed to a failure in neural crest cell (NCC) development during the embryonic stage. The colonization of the intestine by NCCs is a process finely controlled by a wide and complex gene regulatory system. Several genes have been associated with HSCR, but many aspects still remain poorly understood. The present study is focused on deciphering the PAX6 interaction network during enteric nervous system (ENS) formation. A combined experimental and computational approach was performed to identify PAX6 direct targets, as well as gene networks shared among such targets as potential susceptibility factors for HSCR. As a result, genes related to PAX6 either directly (RABGGTB and BRD3) or indirectly (TGFB1, HRAS, and GRB2) were identified as putative genes associated with HSCR. Interestingly, GRB2 is involved in the RET/GDNF/GFRA1 signaling pathway, one of the main pathways implicated in the disease. Our findings represent a new contribution to advance in the knowledge of the genetic basis of HSCR. The investigation of the role of these genes could help to elucidate their implication in HSCR onset. MDPI 2020-11-28 /pmc/articles/PMC7730166/ /pubmed/33260622 http://dx.doi.org/10.3390/ijms21239061 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Villalba-Benito, Leticia
Torroglosa, Ana
Luzón-Toro, Berta
Fernández, Raquel María
Moya-Jiménez, María José
Antiñolo, Guillermo
Borrego, Salud
ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title_full ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title_fullStr ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title_full_unstemmed ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title_short ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease
title_sort chip-seq-based approach in mouse enteric precursor cells reveals new potential genes with a role in enteric nervous system development and hirschsprung disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730166/
https://www.ncbi.nlm.nih.gov/pubmed/33260622
http://dx.doi.org/10.3390/ijms21239061
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