Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning

Waskiewicz, A.J., Rikhof, H.A., Hernandez, R.E., and Moens, C.B.
Development (Cambridge, England)   128(21): 4139-4151 (Journal)
Registered Authors
Hernandez, Rafael, Moens, Cecilia, Rikhof, Holly, Waskiewicz, Andrew
Hox, Meis, Pbx, hindbrain, patterning, segmentation, rhombomere, zebrafish, cooperative DNA binding, homeodomain proteins, nuclear localization, homeobox genes, hox proteins, homeotic transformation, segmental expression, vertebrate hindbrain, ectopic expression, export signals
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Genes, Dominant
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins
  • Rhombencephalon/embryology*
  • Transcription Factors/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
11684652 Full text @ Development
Homeodomain-containing Hox proteins regulate segmental identity in Drosophila in concert with two partners known as Extradenticle (Exd) and Homothorax (Hth). These partners are themselves DNA-binding, homeodomain proteins, and probably function by revealing the intrinsic specificity of Hox proteins. Vertebrate orthologs of Exd and Hth, known as Pbx and Meis (named for a myeloid ecotropic leukemia virus integration site), respectively, are encoded by multigene families and are present in multimeric complexes together with vertebrate Hox proteins. Previous results have demonstrated that the zygotically encoded Pbx4/Lazarus (Lzr) protein is required for segmentation of the zebrafish hindbrain and proper expression and function of Hox genes. We demonstrate that Meis functions in the same pathway as Pbx in zebrafish hindbrain development, as expression of a dominant-negative mutant Meis results in phenotypes that are remarkably similar to that of lzr mutants. Surprisingly, expression of Meis protein partially rescues the lzr(-) phenotype. Lzr protein levels are increased in embryos overexpressing Meis and are reduced for lzr mutants that cannot bind to Meis. This implies a mechanism whereby Meis rescues lzr mutants by stabilizing maternally encoded Lzr. Our results define two functions of Meis during zebrafish hindbrain segmentation: that of a DNA-binding partner of Pbx proteins, and that of a post-transcriptional regulator of Pbx protein levels.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes