Regulation of dharma/bozozok by the Wnt Pathway

Abstract

The zebrafish homeobox gene dharma/bozozok (boz) is required for the formation and/or function of the Nieuwkoop center and the subsequent induction of the Spemann organizer. dharma is expressed soon after the midblastula transition in the dorsal blastomeres and the dorsal yolk syncytial layer (YSL). We found that the expression of dharma was upregulated or ectopically induced by misexpression of a Wnt protein and cytoplasmic components of the Wnt signaling pathway and downregulated by the expression of dominant-negative Tcf3. A 1.4-kbp fragment of the dharma promoter region contains consensus sequences for Tcf/Lef binding sites. This promoter region recapitulated the Wnt-dependent and dorsal dharma expression pattern when it was fused to luciferase or GFP. Deletion and point mutant analyses revealed that the Tcf/Lef binding sites were required to drive this expression pattern. These data established that dharma/boz functions between the dorsal determinants-mediated Wnt signals and the formation of the Nieuwkoop center.

Zebrafish admp is required to restrict the size of the organizer and to promote posterior and ventral development

“…Here, we report the isolation and characterization of a zebrafish admp homologue. We show that its expression is posi-tively regulated by the Bmp repressor Boz (Koos and Ho, 1999;Ryu et al, 2001), but that Admp itself has effects opposite to those of Boz. Thus, the phenotype of boz mutants can be phenocopied by overexpression of admp, whereas boz overexpression phenocopies traits of admp morphants.…”

Wnt Signaling in Vertebrate Axis Specification

“…b-catenin activates several major targets in Xenopus embryos that are responsible for Spemann organizer formation. Activation of many organizerspecific genes depends on functional TCF sites in their promoters (Brannon et al 1997;Laurent et al 1997;McKendry et al 1997;Fan et al 1998;Ryu et al 2001;Leung et al 2003). These early b-catenin targets include Nodal group genes that are essential for dorsal mesoderm formation in frogs, zebrafish, and mammals (Conlon et al 1994;Feldman et al 1998;Osada and Wright 1999;Takahashi et al 2000;Yang et al 2002;Hilton et al 2003;Zhang et al 2003).…”

“…These early b-catenin targets include Nodal group genes that are essential for dorsal mesoderm formation in frogs, zebrafish, and mammals (Conlon et al 1994;Feldman et al 1998;Osada and Wright 1999;Takahashi et al 2000;Yang et al 2002;Hilton et al 2003;Zhang et al 2003). Besides Nodals, other direct targets of b-catenin are Siamois and Twin in Xenopus (Lemaire et al 1995;Brannon et al 1997;Laurent et al 1997;Fan et al 1998), and Bozozok/ Dharma/Nieuwkoid in zebrafish (Ryu et al 2001), which are required for organizer formation ( Fig. 2; Table 1) (Fan and Sokol 1997;Kessler 1997;Koos and Ho 1998;Yamanaka et al 1998;Fekany et al 1999).…”

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

“…Maternally supplied ␤-catenin initiates the transcription of dorsal determining genes, like boz and the Nodals sqt and cyc (Ryu et al, 2001;Dougan et al, 2003;Leung et al, 2003b). Normal initiation of dpr genes, therefore, might rely directly on ␤-catenin or its downstream target genes.…”

“…The accumulation of ␤-catenin on the future dorsal side leads to the expression of genes of the dorsal organizer and, in at least one case, potentiation of the action of an organizer protein (Kelly et al, 2000;Ryu et al, 2001;Solnica-Krezel and Driever, 2001;Yamashita et al, 2002;Dougan et al, 2003). Organizer genes promote dorsal axis formation in three important ways: by antagonizing the activity of ventralizing genes, by establishing dorsal mesendoderm, and by promoting proper gastrulation movements.…”