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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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9061 |
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| author | Leticia Villalba-Benito Ana Torroglosa Berta Luzón-Toro Raquel María Fernández María José Moya-Jiménez Guillermo Antiñolo Salud Borrego |
| author_facet | Leticia Villalba-Benito Ana Torroglosa Berta Luzón-Toro Raquel María Fernández María José Moya-Jiménez Guillermo Antiñolo Salud Borrego |
| author_sort | Leticia Villalba-Benito |
| collection | DOAJ |
| 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 (<i>RABGGTB</i> and <i>BRD3</i>) or indirectly (<i>TGFB1</i>, <i>HRAS</i>, and <i>GRB2</i>) were identified as putative genes associated with HSCR. Interestingly, <i>GRB2</i> 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. |
| first_indexed | 2024-03-10T14:28:18Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:28:18Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8c805f45ca8a403ca41aaf451132dd3d2023-11-20T22:47:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123906110.3390/ijms21239061ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung DiseaseLeticia Villalba-Benito0Ana Torroglosa1Berta Luzón-Toro2Raquel María Fernández3María José Moya-Jiménez4Guillermo Antiñolo5Salud Borrego6Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainDepartment of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainDepartment of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainDepartment of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainDepartment of Pediatric Surgery, University Hospital Virgen del Rocío, 41013 Seville, SpainDepartment of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainDepartment of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainHirschsprung 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 (<i>RABGGTB</i> and <i>BRD3</i>) or indirectly (<i>TGFB1</i>, <i>HRAS</i>, and <i>GRB2</i>) were identified as putative genes associated with HSCR. Interestingly, <i>GRB2</i> 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.https://www.mdpi.com/1422-0067/21/23/9061Hirschsprung diseaseChIP-seqgene expression profilingsequence analysis<i>PAX6</i> |
| spellingShingle | Leticia Villalba-Benito Ana Torroglosa Berta Luzón-Toro Raquel María Fernández María José Moya-Jiménez Guillermo Antiñolo Salud Borrego ChIP-Seq-Based Approach in Mouse Enteric Precursor Cells Reveals New Potential Genes with a Role in Enteric Nervous System Development and Hirschsprung Disease International Journal of Molecular Sciences Hirschsprung disease ChIP-seq gene expression profiling sequence analysis <i>PAX6</i> |
| 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 | Hirschsprung disease ChIP-seq gene expression profiling sequence analysis <i>PAX6</i> |
| url | https://www.mdpi.com/1422-0067/21/23/9061 |
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