Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity
| Autor: | Wolfgang Wurst, Luca Giovanni Di Giovannantonio, Dario Acampora, Michela Di Salvio, Antonio Simeone, Nilima Prakash, Daniela Omodei, Alessandra Pierani |
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| Přispěvatelé: | Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', CNR (IGB), Institute of Genetics and Biophysics, CEINGE Biotecnologie Avanzate s.c.a.r.l., CEINGE - Biotecnologie Avanzate, Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Lehrstuhl für Entwicklungsgenetik, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Italian Association for Cancer Research (AIRC) grant number IG-2013 n.14512, Association pour la Recherche sur le Cancer (ARC) grant number SFI 2011 1203674, Centre National de la Recherche Scientifique (CNRS), Technische Universität München [München] (TUM), Università degli Studi di Roma 'La Sapienza' [Rome]-Università degli studi di Napoli Federico II |
| Rok vydání: | 2014 |
| Předmět: |
Cerebellum
Mouse metabolism [Neural Stem Cells] Mice Progenitor fate Otx2 Dorsal mesencephalon Neural Stem Cells Mesencephalon Pregnancy cytology [Embryonic Stem Cells] metabolism [Embryonic Stem Cells] metabolism [Transcription Factors] cytology [Neural Stem Cells] [SDV.BDD]Life Sciences [q-bio]/Development Biology Mice Knockout metabolism [Mesencephalon] Otx Transcription Factors Neurogenesis metabolism [Otx Transcription Factors] PAX7 Transcription Factor Cell Differentiation metabolism [PAX7 Transcription Factor] Anatomy metabolism [Cerebellum] genetics [Transcription Factors] Cell biology embryology [Mesencephalon] medicine.anatomical_structure embryology [Organizers Embryonic] Female metabolism [Organizers Embryonic] embryology [Cerebellum] Mice Transgenic Context (language use) Pax7 protein mouse Biology Cell fate determination ddc:570 medicine Animals Progenitor cell Molecular Biology Embryonic Stem Cells Body Patterning deficiency [Transcription Factors] Progenitor Neuroectoderm Organizers Embryonic Otx2 protein mouse Granule cell Mice Mutant Strains deficiency [Otx Transcription Factors] Zic1 protein mouse Mutation genetics [Otx Transcription Factors] Transcription Factors Developmental Biology |
| Zdroj: | Development 141, 377-388 (2014) Development (Cambridge, England) Development (Cambridge, England), Company of Biologists, 2014, 141 (2), pp.377-88. ⟨10.1242/dev.102954⟩ Development Development (Dublin, 1970) 141 (2014): 377. doi:10.1242/dev.102954 info:cnr-pdr/source/autori:Di Giovannantonio LG, Di Salvio M, Omodei D, Prakash N, Wurst W, Pierani A, Acampora D, Simeone A./titolo:Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity./doi:10.1242%2Fdev.102954/rivista:Development (Dublin, 1970)/anno:2014/pagina_da:/pagina_a:377/intervallo_pagine:377/volume:141 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.102954 |
| Popis: | International audience; During embryonic development, the rostral neuroectoderm is regionalized into broad areas that are subsequently subdivided into progenitor compartments with specialized identity and fate. These events are controlled by signals emitted by organizing centers and interpreted by target progenitors, which activate superimposing waves of intrinsic factors restricting their identity and fate. The transcription factor Otx2 plays a crucial role in mesencephalic development by positioning the midbrain-hindbrain boundary (MHB) and its organizing activity. Here, we investigated whether Otx2 is cell-autonomously required to control identity and fate of dorsal mesencephalic progenitors. With this aim, we have inactivated Otx2 in the Pax7(+) dorsal mesencephalic domain, previously named m1, without affecting MHB integrity. We found that the Pax7(+) m1 domain can be further subdivided into a dorsal Zic1(+) m1a and a ventral Zic1(-) m1b sub-domain. Loss of Otx2 in the m1a (Pax7(+) Zic1(+)) sub-domain impairs the identity and fate of progenitors, which undergo a full switch into a coordinated cerebellum differentiation program. By contrast, in the m1b sub-domain (Pax7(+) Zic1(-)) Otx2 is prevalently required for post-mitotic transition of mesencephalic GABAergic precursors. Moreover, genetic cell fate, BrdU cell labeling and Otx2 conditional inactivation experiments indicate that in Otx2 mutants all ectopic cerebellar cell types, including external granule cell layer (EGL) precursors, originate from the m1a progenitor sub-domain and that reprogramming of mesencephalic precursors into EGL or cerebellar GABAergic progenitors depends on temporal sensitivity to Otx2 ablation. Together, these findings indicate that Otx2 intrinsically controls different aspects of dorsal mesencephalic neurogenesis. In this context, Otx2 is cell-autonomously required in the m1a sub-domain to suppress cerebellar fate and promote mesencephalic differentiation independently of the MHB organizing activity. |
| Databáze: | OpenAIRE |
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