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The caudal limit of Otx2 expression positions the isthmic organizer

Author

Listed:
  • Vania Broccoli

    (GSF-Research Centre for Environment and Health, Institute of Mammalian Genetics
    Max Planck Institute of Psychiatry
    San Raffaele Biomedical Science Park)

  • Edoardo Boncinelli

    (DIBIT-HSRaffaele)

  • Wolfgang Wurst

    (GSF-Research Centre for Environment and Health, Institute of Mammalian Genetics
    Max Planck Institute of Psychiatry)

Abstract

The homeobox gene Otx2 is expressed in the anterior neural tube with a sharp limit at the midbrain/hindbrain junction (the isthmic organizer)1. Otx2 inactivation experiments have shown that this gene is essential for the development of its expression domain2. Here we investigate whether the caudal limit of Otx2 expression is instrumental in positioning the isthmic organizer and in specifying midbrain versus hindbrain fate, by ectopically expressing Otx2 in the presumptive anterior hindbrain using a knock-in strategy into the En1 locus. Transgenic offspring display a cerebellar ataxia. Morphological and histological studies of adult transgenic brains reveal that most of the anterior cerebellar vermis is missing, whereas the inferior colliculus is complementarily enlarged. During early neural pattern formation expression of the midbrain markers Wnt1 and Ephrin-A5, the isthmic organizer markers Pax2 and Fgf-8 and the hindbrain marker Gbx2 are shifted caudally in the presumptive hindbrain territory. These findings show that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain.

Suggested Citation

  • Vania Broccoli & Edoardo Boncinelli & Wolfgang Wurst, 1999. "The caudal limit of Otx2 expression positions the isthmic organizer," Nature, Nature, vol. 401(6749), pages 164-168, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6749:d:10.1038_43670
    DOI: 10.1038/43670
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    1. Seppe Goovaerts & Hanne Hoskens & Ryan J. Eller & Noah Herrick & Anthony M. Musolf & Cristina M. Justice & Meng Yuan & Sahin Naqvi & Myoung Keun Lee & Dirk Vandermeulen & Heather L. Szabo-Rogers & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Muyesier Maimaitili & Muwan Chen & Fabia Febbraro & Ekin Ucuncu & Rachel Kelly & Jonathan Christos Niclis & Josefine Rågård Christiansen & Noëmie Mermet-Joret & Dragos Niculescu & Johanne Lauritsen & , 2023. "Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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