Epithelial Splicing Regulatory Protein 1 (ESRP1) is a new regulator of stomach smooth muscle development and plasticity.
In vertebrates, stomach smooth muscle development is a complex process that involves the tight transcriptional or post-transcriptional regulation of different signalling pathways. Here, we identified the RNA-binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) as an early marker of developing and undifferentiated stomach mesenchyme. Using a gain-of-function approach, we found that in chicken embryos, sustained expression of ESRP1 impairs stomach smooth muscle cell (SMC) differentiation and FGFR2 splicing profile. ESRP1 overexpression in primary differentiated stomach SMCs induced their dedifferentiation, promoted specific-FGFR2b splicing and decreased FGFR2c-dependent activity. Moreover, co-expression of ESRP1 and RBPMS2, another RNA-binding protein that regulates SMC plasticity and Bone Morphogenetic Protein (BMP) pathway inhibition, synergistically promoted SMC dedifferentiation. Finally, we also demonstrated that ESRP1 interacts with RBPMS2 and that RBPMS2-mediated SMC dedifferentiation requires ESRP1. Altogether, these results show that ESRP1 is expressed also in undifferentiated stomach mesenchyme and demonstrate its role in SMC development and plasticity.
PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295 Montpellier cedex 5, France.
Sébastien
S
Sagnol
PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295 Montpellier cedex 5, France.
Stéphane
S
Marchal
Centre de Biochimie Structurale, CNRS UMR 5048, INSERM U1054, University of Montpellier, 34295 Montpellier cedex 5, France.
Yinshan
Y
Yang
Centre de Biochimie Structurale, CNRS UMR 5048, INSERM U1054, University of Montpellier, 34295 Montpellier cedex 5, France.
Frédéric
F
Allemand
PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295 Montpellier cedex 5, France. Electronic address: Pascal.de-Santa-Barbara@inserm.fr.
Pascal
P
de Santa Barbara
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005895:Gizzard, Avian / Q000166:cytology / Q000196:embryology*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000196:embryology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D061251:Primary Cell Culture; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D012326:RNA Splicing / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D030161:Avian Proteins; D018076:DNA, Complementary; C539364:ESRP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C078114:FGFR2 protein, chicken; D020794:Receptor Protein-Tyrosine Kinases
Chick; ESRP1; FGF pathway; Gastrointestinal tract; RNA-binding protein; Smooth muscle