Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation

We identified a zebrafish homologue of Dickkopf-1 (Dkk1), which was previou sly identified in Xenopus as a Wnt inhibitor with potent head-inducing acti vity. Zebrafish dkk1 is expressed in the dorsal marginal blastoderm and als o in the dorsal yolk syncytial layer after mid-blastula transition. At late r blastula stages, the expression expands to the entire blastoderm margin. During gastrulation, dkk1-expressing cells are confined to the embryonic sh ield and later to the anterior axial mesendoderm, prospective prechordal pl ate. Embryos, in which dkk1 was ectopically expressed, exhibited enlarged f orebrain, eyes, and axial mesendoderm such as prechordal plate and notochor d. dkk1 expression in the dorso-anterior mesendoderm during gastrulation wa s prominently reduced in zebrafish mutants bozozok (boz), squint (sqt), and one-eyed pinhead (oep), which all display abnormalities in the formation a nd function of the Spemann organizer and axial mesendoderm. dkk1 expression was normal in these embryos during the blastula period, indicating that zy gotic functions of these genes are required for maintenance but not establi shment of dkk1 expression. Overexpression of dkk1 suppressed defects in the development of forebrain, eyes, and notochord in boz mutants. Overexpressi on of dkk1 promoted anterior neuroectoderm development in the embryos injec ted with antivin RNA, which lack most of the mesoderm and endoderm, suggest ing that Dkk1 can affect regionalization of neuroectoderm independently of dorso-anterior mesendoderm. These data indicate that Dkk1, expressed in dor sal mesendoderm, functions in the formation of both the anterior nervous sy stem and the axial mesendoderm in zebrafish. (C) 2000 Academic Press.