Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish

Abstract

Members of the Wnt family of extracellular proteins play essential roles during many phases of vertebrate embryonic development. The molecular mechanism of their action involves a complex cascade of intracellular signaling events, which remains to be understood completely. Recently, two novel cytoplasmic modulators of Wnt signaling, Frodo and Dapper, were identified in Xenopus. We report isolation of their homologs in zebrafish, and show that these genes, frd1 and frd2, are expressed in restricted domains during embryogenesis. Both genes are expressed during early gastrulation in the future mesendoderm, and continue to be expressed in distinct patterns in the forming neurectoderm and mesoderm. Comparative sequence analysis and similar expression patterns argue that frd1 is the zebrafish ortholog of Frodo and Dapper, whereas frd2 is a more divergent member of the same family. Our data suggest important roles for zebrafish frd1 and frd2 in patterning the neural plate and several mesodermal derivatives.

Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2

“…Because initiation of dpr1 and dpr2 expression does not require Nodal signaling, my data do not support the hypothesis of Zhang et al (2004) that dpr2 expression is initiated and solely regulated throughout development by Nodal signaling. Given the complex expression patterns of dpr1 and dpr2 later in development (Gillhouse et al, 2004;Zhang et al, 2004;Waxman et al, 2004), it is likely that later dpr expression patterns require input from multiple signaling pathways.…”

“…In different assays Dpr/Frd members can act as either inhibitors or activators of Wnt/␤-catenin signaling (Cheyette et al, 2002;Gloy et al, 2002;Hikasa and Sokol, 2004). All currently sequenced vertebrate genomes, except Xenopus laevis, have two conserved Dpr paralogs, Dpr1 and Dpr2 (Gillhouse et al, 2004;Waxman et al, 2004). A genome duplication event in Xenopus laevis has led to two proteins orthologous to the Dpr1 isoform, XDpr1a and Frodo/XDpr1b, that are 90% identical to each other (Waxman et al, 2004), whereas Xenopus Dpr2 orthologs have not been identified yet.…”

“…We and others have characterized expression of zebrafish dpr1/frd1 and dpr2/frd2, here referred to as dpr1 and dpr2 (Gillhouse et al, 2004;Zhang, 2004;Waxman et al, 2004). Both dpr1 and dpr2 are expressed on the prospective dorsal side of the embryo shortly after the initiation of zygotic transcription (Zhang, 2004;Waxman et al, 2004).…”

Three Dact gene family members are expressed during embryonic development and in the adult brains of mice

“…Based on sequence similarity, Dact1, which maps to mouse chromosome 12D1, is the closest mammalian homolog to the Dpr and Frodo sequences identified in Xenopus and corresponds to the mammalian Dpr1 and Frd1 genes reported in the literature (Cheyette et al, 2002;Katoh and Katoh, 2003;Yau et al, 2004;Zhang et al, 2004;Brott and Sokol, 2005b;Hunter et al, 2005). Dact2, which is most closely related to the frd2/dpr2 sequences identified in zebrafish (Gillhouse et al, 2004;Waxman et al, 2004), maps to mouse chromosome 17A2. Dact3, which has not been described previously, maps to mouse chromosome 7A2.…”

“…Because of its central role in Wnt signal transduction, efforts have been made to identify the direct binding partners of Dvl. One such protein, which binds to the Dvl PDZ domain by means of a conserved C-terminal PDZ-binding motif (Cheyette et al, 2002), has alternately been named Dapper (Dpr), Frodo (Frd), THYEX3, HNG3, MTNG3, and Dact in various organisms (Cheyette et al, 2002;Gloy et al, 2002;Gillhouse et al, 2004;Yau et al, 2004;Zhang et al, 2004;Hunter et al, 2005;Katoh, 2005). For simplicity, hereafter we use the symbol "Dact" assigned by the Human Genome Organization Nomenclature Committee and the Mouse Genome Informatics website for all members of this gene family.…”