Lu, F.I., Thisse, C., and Thisse, B. (2011) Identification and mechanism of regulation of the zebrafish dorsal determinant. Proceedings of the National Academy of Sciences of the United States of America. 108(38):15876-80.
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.