Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost

Kurokawa, D., Sakurai, Y., Inoue, A., Nakayama, R., Takasaki, N., Suda, Y., Miyake, T., Amemiya, C.T., and Aizawa, S.
Proceedings of the National Academy of Sciences of the United States of America   103(51): 19350-19355 (Journal)
Registered Authors
Amemiya, Chris
anterior neuroectoderm, coelacanth, enhancer, tetrapod, chondrichthyes
MeSH Terms
  • Animals
  • Base Sequence
  • Brain/embryology*
  • Brain/metabolism
  • Cloning, Molecular
  • Ectoderm/metabolism*
  • Embryo, Mammalian/metabolism
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic/genetics
  • Evolution, Molecular*
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Morphogenesis/genetics*
  • Otx Transcription Factors/genetics*
  • Otx Transcription Factors/metabolism*
  • Phylogeny*
  • Takifugu
  • Vertebrates/embryology*
  • Vertebrates/genetics*
  • Vertebrates/metabolism
  • Zebrafish
17159156 Full text @ Proc. Natl. Acad. Sci. USA
Otx2 is a paired type homeobox gene that plays essential roles in each step and site of head development in vertebrates. In the mouse, Otx2 expression in the anterior neuroectoderm is regulated primarily by two distinct enhancers: anterior neuroectoderm (AN) and forebrain/midbrain (FM) enhancers at 92 kb and 75 kb 5'of the Otx2 locus, respectively. The AN enhancer has activity in the entire anterior neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm. In tetrapods, both AN and FM enhancers are conserved, whereas the AN region is missing in teleosts, despite overt Otx2 expression in the anterior neuroectoderm. Here, we show that zebrafish and fugu FM regions drive expression not only in the forebrain and midbrain but also in the anterior neuroectoderm at headfold stage. The analysis of coelacanth and skate genomic Otx2 orthologues suggests that the utilization of the two enhancers, AN and FM, is an ancestral condition. In contrast, the AN enhancer has been specifically lost in the teleost lineage with a compensatory establishment of AN activity within the FM enhancer. Furthermore, the AN activity in the fish FM enhancer was established by recruiting upstream factors different from those that direct the tetrapod AN enhancer, yet zebrafish FM enhancer is active in both mouse and zebrafish anterior neuroectoderm at the headfold stage.
Genes / Markers
Figure Gallery
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes