Repression of Irs2 by let‐7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium
| Autor: | Yuki Nomura, Virginia Fernández, Maria Ángeles Martínez-Martínez, Adrián Cárdenas, Rafael Soler, José P. López-Atalaya, Ugo Tomasello, Federico Calegari, Víctor Borrell, Anna Prieto-Colomina, Martina Dori |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Research Council, European Commission, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundación Tatiana Pérez de Guzmán el Bueno |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Telencephalon
p53 PAX6 Transcription Factor Neurogenesis ectopia Cellular homeostasis Apoptosis Nerve Tissue Proteins Biology Article General Biochemistry Genetics and Molecular Biology Transcriptome Mice 03 medical and health sciences 0302 clinical medicine microRNA Animals Homeostasis Humans cancer Progenitor cell Molecular Biology Cell Proliferation 030304 developmental biology 0303 health sciences General Immunology and Microbiology Stem Cells General Neuroscience Adherens Junctions Articles RNA Biology Embryonic stem cell Pax6 Cell biology Mice Inbred C57BL Repressor Proteins Neuroepithelial cell MicroRNAs apical adherens junction Forebrain Insulin Receptor Substrate Proteins PAX6 030217 neurology & neurosurgery Transcription Factors Neuroscience |
| Zdroj: | The EMBO Journal Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Structural integrity and cellular homeostasis of the embryonic stem cell niche are critical for normal tissue development. In the telencephalic neuroepithelium, this is controlled in part by cell adhesion molecules and regulators of progenitor cell lineage, but the specific orchestration of these processes remains unknown. Here, we studied the role of microRNAs in the embryonic telencephalon as key regulators of gene expression. By using the early recombiner Rx‐Cre mouse, we identify novel and critical roles of miRNAs in early brain development, demonstrating they are essential to preserve the cellular homeostasis and structural integrity of the telencephalic neuroepithelium. We show that Rx‐Cre;DicerF/F mouse embryos have a severe disruption of the telencephalic apical junction belt, followed by invagination of the ventricular surface and formation of hyperproliferative rosettes. Transcriptome analyses and functional experiments in vivo show that these defects result from upregulation of Irs2 upon loss of let‐7 miRNAs in an apoptosis‐independent manner. Our results reveal an unprecedented relevance of miRNAs in early forebrain development, with potential mechanistic implications in pediatric brain cancer. V.F. was recipient of an FPI fellowship from the Spanish State Research Agency (AEI), and A.P.‐C. was recipient of a predoctoral fellowship from Fundación Tatiana Pérez de Guzmán el Bueno. This work was supported by grants to V.B. from AEI (SAF2015‐69168‐R, PGC2018‐102172‐B‐I00) and European Research Council (309633). V.B. acknowledges financial support from the AEI, through the “Severo Ochoa” Program for Centers of Excellence in R&D (Ref. SEV‐2017‐0723). |
| Databáze: | OpenAIRE |
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