Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity. (Articolo in rivista)

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  • Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity. (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1242/dev.102954 (literal)
Alternative label
  • Di Giovannantonio LG, Di Salvio M, Omodei D, Prakash N, Wurst W, Pierani A, Acampora D, Simeone A. (2014)
    Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity.
    in Development (Dublin, 1970)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Di Giovannantonio LG, Di Salvio M, Omodei D, Prakash N, Wurst W, Pierani A, Acampora D, Simeone A. (literal)
Pagina fine
  • 377 (literal)
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  • 141 (literal)
Rivista
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  • 388 (literal)
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  • 2 (literal)
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  • PubMe (literal)
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  • Institute of Genetics and Biophysics \"Adriano Buzzati-Traverso\", CNR, Via P. Castellino 111, 80131 Naples, Italy. CEINGE Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy. Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), and Technische Universität München-Weihenstephan, Lehrstuhl für Entwicklungsgenetik, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Standort München, Schillerstrasse 44, D-80336 München, Germany. Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 München, Germany. Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France. IRCCS Neuromed, 86077 Pozzilli (IS), Italy. (literal)
Titolo
  • Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity. (literal)
Abstract
  • 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. (literal)
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