Wnt/β-catenin pathway and cell adhesion ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders
Auteur(s) :
El Khouri, E. [Auteur]
Ghoumid, Jamal [Auteur]
Maladies RAres du DÉveloppement embryonnaire et du Métabolisme : du phénotype au génotype et à la Fonction (RADEME) - ULR 7364
Haye, Damien [Auteur]
Giuliano, F. [Auteur]
Drevillon, L. [Auteur]
Briand-Suleau, Audrey [Auteur]
De La Grange, P. [Auteur]
Nau, V. [Auteur]
Gaillon, T. [Auteur]
Bienvenu, Thierry [Auteur]
Jacquemin-Sablon, H. [Auteur]
Goossens, M. [Auteur]
Amselem, S. [Auteur]
Giurgea, Irina [Auteur]
Ghoumid, Jamal [Auteur]
Maladies RAres du DÉveloppement embryonnaire et du Métabolisme : du phénotype au génotype et à la Fonction (RADEME) - ULR 7364
Haye, Damien [Auteur]
Giuliano, F. [Auteur]
Drevillon, L. [Auteur]
Briand-Suleau, Audrey [Auteur]
De La Grange, P. [Auteur]
Nau, V. [Auteur]
Gaillon, T. [Auteur]
Bienvenu, Thierry [Auteur]
Jacquemin-Sablon, H. [Auteur]
Goossens, M. [Auteur]
Amselem, S. [Auteur]
Giurgea, Irina [Auteur]
Titre de la revue :
Molecular psychiatry
Nom court de la revue :
Mol Psychiatry
Date de publication :
2021-04-19
ISSN :
1476-5578
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Among the genetic factors playing a key role in the etiology of intellectual disabilities (IDs) and autism spectrum disorders (ASDs), several encode RNA-binding proteins (RBPs). In this study, we deciphered the molecular ...
Lire la suite >Among the genetic factors playing a key role in the etiology of intellectual disabilities (IDs) and autism spectrum disorders (ASDs), several encode RNA-binding proteins (RBPs). In this study, we deciphered the molecular and cellular bases of ID-ASD in a patient followed from birth to the age of 21, in whom we identified a de novo CSDE1 (Cold Shock Domain-containing E1) nonsense variation. CSDE1 encodes an RBP that regulates multiple cellular pathways by monitoring the translation and abundance of target transcripts. Analyses performed on the patient's primary fibroblasts showed that the identified CSDE1 variation leads to haploinsufficiency. We identified through RNA-seq assays the Wnt/β-catenin signaling and cellular adhesion as two major deregulated pathways. These results were further confirmed by functional studies involving Wnt-specific luciferase and substrate adhesion assays. Additional data support a disease model involving APC Down-Regulated-1 (APCDD1) and cadherin-2 (CDH2), two components of the Wnt/β-catenin pathway, CDH2 being also pivotal for cellular adhesion. Our study, which relies on both the deep phenotyping and long-term follow-up of a patient with CSDE1 haploinsufficiency and on ex vivo studies, sheds new light on the CSDE1-dependent deregulated pathways in ID-ASD.Lire moins >
Lire la suite >Among the genetic factors playing a key role in the etiology of intellectual disabilities (IDs) and autism spectrum disorders (ASDs), several encode RNA-binding proteins (RBPs). In this study, we deciphered the molecular and cellular bases of ID-ASD in a patient followed from birth to the age of 21, in whom we identified a de novo CSDE1 (Cold Shock Domain-containing E1) nonsense variation. CSDE1 encodes an RBP that regulates multiple cellular pathways by monitoring the translation and abundance of target transcripts. Analyses performed on the patient's primary fibroblasts showed that the identified CSDE1 variation leads to haploinsufficiency. We identified through RNA-seq assays the Wnt/β-catenin signaling and cellular adhesion as two major deregulated pathways. These results were further confirmed by functional studies involving Wnt-specific luciferase and substrate adhesion assays. Additional data support a disease model involving APC Down-Regulated-1 (APCDD1) and cadherin-2 (CDH2), two components of the Wnt/β-catenin pathway, CDH2 being also pivotal for cellular adhesion. Our study, which relies on both the deep phenotyping and long-term follow-up of a patient with CSDE1 haploinsufficiency and on ex vivo studies, sheds new light on the CSDE1-dependent deregulated pathways in ID-ASD.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Collections :
Date de dépôt :
2021-09-02T07:01:01Z