Identification and mechanism of regulation of the zebrafish dorsal determinant

Lu, F.I., Thisse, C., and Thisse, B.
Proceedings of the National Academy of Sciences of the United States of America   108(38): 15876-80 (Journal)
Registered Authors
Lu, Fu-I, Thisse, Bernard, Thisse, Christine
asymmetry, teleost
MeSH Terms
  • Animals
  • Base Sequence
  • Body Patterning/genetics
  • Cytoskeletal Proteins/genetics*
  • Cytoskeletal Proteins/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Glycoproteins/genetics*
  • Glycoproteins/metabolism
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • In Situ Hybridization
  • Male
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Morpholinos/genetics
  • Nocodazole/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Tubulin Modulators/pharmacology
  • Wnt Proteins/genetics*
  • Wnt Proteins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • beta Catenin/genetics
  • beta Catenin/metabolism
21911385 Full text @ Proc. Natl. Acad. Sci. USA

In vertebrates, the animal–vegetal axis is determined during oogenesis and at ovulation, the egg is radially symmetric. In anamniotes, following fertilization, a microtubule-dependent movement leads to the displacement of maternal dorsal determinants from the vegetal pole to the future dorsal side of the embryo, providing the initial breaking of radial symmetry [Weaver C, Kimelman D (2004) Development 131:3491–3499]. These dorsal determinants induce β-catenin nuclear translocation in dorsal cells of the blastula. Previous work in amphibians has shown that secreted Wnt11/5a complexes, regulated by the Wnt antagonist Dkk-1, are required for the initiation of embryonic axis formation [Cha et al. (2009) Curr Biol 29:1573–1580]. In the current study, we determined that the vegetal maternal dorsal determinant in fish is not the Wnt11/5a complex but the canonical Wnt, Wnt8a. Translation of this mRNA and secretion of the Wnt8a protein result in a dorsal-to-ventral gradient of Wnt stimulation, extending across the entire embryo. This gradient is counterbalanced by two Wnt inhibitors, Sfrp1a and Frzb. These proteins are essential to restrict the activation of the canonical Wnt pathway to the dorsal marginal blastomeres by defining the domain where the Wnt8a activity gradient is above the threshold value necessary for triggering the canonical β-catenin pathway. In summary, this study establishes that the zebrafish maternal dorsal determinant, Wnt8a, is required to localize the primary dorsal center, and that the extent of this domain is defined by the activity of two maternally provided Wnt antagonists, Sfrp1a and Frzb.

Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes