EMB is essential for enteric nervous system development mediated by PI3K signaling
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Le résumé fourni par la source
BACKGROUND: The enteric nervous system (ENS), which arises from enteric neural crest cells (ENCCs), plays important roles in many aspects of gastrointestinal tract function, including motility, secretions, blood flow and hormone release. Defects in ENS development could lead to a broad range of disorders, including Hirschsprung's disease (HSCR), which is characterized by missing nerve cells in the distal segment of the colon. Here, we identify EMB as an evolutionarily conserved regulator of ENS development. METHODS: We first examined EMB expression in human and mouse intestines using scRNA-seq data and immunofluorescence staining. To investigate its role in ENS development, we constructed Emb-knockout zebrafish and mouse models. To explore the underlying mechanisms, we focused on ENCCs and analyzed their proliferation and migration using migration assays in explant guts and organoid cultures. Finally, we assessed rare EMB variants in a cohort of HSCR patients. RESULTS: In zebrafish, loss of emb leads to a decrease number of enteric neurons and impaired intestinal transit ability. In mice, knockout of Emb causes HSCR-like phenotypes and defects. In vitro experiments, including explant mouse gut and organoid cultures, show that EMB is required for both the proliferation and migration of ENCCs. Mechanistically, EMB binds to and recruits the phosphatase complex PP2A to the cellular membrane to facilitate the activation of PI3K-AKT pathway, thereby promoting ENCCs development. Indeed, application of PI3K or AKT agonists partially restores the ENS developmental defects in zebrafish emb mutants. Furthermore, rare variants of EMB may potentially contribute to the pathology of HSCR in humans. CONCLUSIONS: EMB is required for ENS development by regulating the proliferation and migration of the ENCCs. Mechanistically, EMB recruits PP2A to the cell membrane, reducing cytoplasmic dephosphorylation activity and promoting the activation of the PI3K signaling pathway.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- EMB is essential for enteric nervous system development mediated by PI3K signaling
- Date Crossref
- 25/09/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Hubei Provincial Center for Disease Control and Prevention pays non établi dans la noticeOrganisme public
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Tongji Hospital pays non établi dans la noticeÉtablissement de santé
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Huazhong University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital of Zhengzhou University Department of Pediatric Surgery pays non établi dans la noticeÉtablissement de santé
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Children's Hospital of Zhejiang University pays non établi dans la noticeÉtablissement de santé
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Wuhan Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Nanjing Children's Hospital Department of Pediatric Surgery pays non établi dans la noticeÉtablissement de santé
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Nanjing Medical University pays non établi dans la noticeUniversité ou école supérieure
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Zunyi Medical University Department of Pediatric Surgery pays non établi dans la noticeUniversité ou école supérieure
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Affiliated Hospital of Zunyi Medical College pays non établi dans la noticeÉtablissement de santé
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Shantou University Department of Pediatric Surgery pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Shantou University Medical College pays non établi dans la noticeÉtablissement de santé
Hubei Provincial Center for Disease Control and Prevention, Tongji Hospital et Huazhong University of Science and Technology, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.