title: A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis.
abstract: The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), whose asymmetric division gives birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Here we show that interfering with codon translation speed triggers ER stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as a physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a contribution of UPR to cell fate acquisition during mammalian brain development.
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laguesse
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Creppe
authors.affiliation: Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Albert-Schweitzer-Campus 1, 48129 Muenster, Germany.
authors.forename: Danny D
authors.initials: DD
authors.lastname: Nedialkova
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Prévot
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Borgs
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Huysseune
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Franco
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Guérin
authors.initials: G
authors.lastname: Duysens
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Krusy
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Gabsang
authors.initials: G
authors.lastname: Lee
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thelen
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: GIGA-Signal Transduction, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Close
authors.affiliation: GIGA-Signal Transduction, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Walloon Excellence in Lifesciences and Biotechnology (WELBIO), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Chariot
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.affiliation: Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Muenster, Germany; Faculty of Medicine, University of Muenster, 48129 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Albert-Schweitzer-Campus 1, 48129 Muenster, Germany.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Leidel
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium. Electronic address: godin@igbmc.fr.
authors.forename: Juliette D
authors.initials: JD
authors.lastname: Godin
authors.affiliation: GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium; Walloon Excellence in Lifesciences and Biotechnology (WELBIO), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium. Electronic address: lnguyen@ulg.ac.be.
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002469:Cell Separation; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D003062:Codon; D004331:Drosophila melanogaster; D053595:Embryonic Stem Cells / Q000166:cytology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011489:Protein Denaturation; D017510:Protein Folding; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D056811:Unfolded Protein Response; D015854:Up-Regulation
chemical_list: D003062:Codon; D009419:Nerve Tissue Proteins; C538729:ELP3 protein, human; C000606524:Elp3 protein, mouse; D051548:Histone Acetyltransferases