Zebrafish Dkk1, induced by the pre-MBT Wnt signaling, is secreted from the prechordal plate and patterns the anterior neural plate

Abstract

mRNA injection into the ventral blastomeres of Xenopus embryos of mRNA encoding Wnt pathway genes induces a secondary axis with complete head structures. To identify target genes of the pre-MBT dorsalization pathway that might be responsible for head formation in zebrafish, we have cloned zebrafish dickkopf1 (dkk1), which is expressed in tissues implicated in head patterning. We found that dkk1 blocks the post-MBT Wnt signaling and dkk1 is a target of the pre-MBT Wnt signaling. Dkk1 overexpression in the prechordal plate suggests that Dkk1, secreted from the prechordal plate, expands the forebrain at the expense of the midbrain in the anterior neural plate. Furthermore, dkk1 acts in parallel to the homeobox gene bozozok and bozozok is required for the maintenance of dkk1 expression. The nodal gene squint is also required for the maintenance of dkk1 expression. Among the mutually dependent target genes of the pre-MBT Wnt signaling, dkk1 plays an important role in patterning the anterior head of zebrafish.

Generation and Characterization of a Transgenic Zebrafish Expressing the Reverse Tetracycline Transactivator

“…3B). These phenotypes are similar to those of Dkk1-expressing embryos displaying an enlarged forebrain at the expense of the midbrain in anteriorized embryos (Shinya et al, 2000). These data suggested that induced expression of Wnt-signaling antagonist DKK1 in F 3 embryos had exerted its proper functions in the regulation of Wnt signaling.…”

DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway

“…Furthermore, our findings suggest that DKK1 participates in a novel negative feedback loop in Wnt signaling, similar to Axin2, which is involved in the segmentation clock during somitogenesis (Yan et al, Jho et al, 2002;Lustig et al, 2002;Aulehla et al, 2003). During early development of Xenopus and zebrafish, pre-MBT Wnt signaling induces DKK1 expression, which is essential for head formation (Glinka et al, 1998;Shinya et al, 2000). Notably, all four of the TCFbinding elements, which are evolutionally conserved between human and mouse, are also found in the zebrafish DKK1 promoter.…”

Function and biological roles of the Dickkopf family of Wnt modulators

“…In zebrafish, Dkk1 is also expressed in organizer derivatives of gastrulating embryos (Hashimoto et al, 2000;Shinya et al, 2000). Overexpression of Dkk1 suppresses defects in the development of forebrain, eyes, and notochord in boz mutants, which have organizer deficiencies.…”