The EGF-CFC Protein One-Eyed Pinhead Is Essential for Nodal Signaling

Abstract

The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically for the formation of the ventral neuroectoderm, endoderm, and prechordal plate. Here we report that embryos lacking both maternal and zygotic Oep activity are defective in germ layer formation, organizer development, and the positioning of the anterior-posterior axis. An identical phenotype is displayed by double mutants for the nodal-related genes squint and cyclops. Mutations in oep eliminate the response to Squint and Cyclops overexpression but are suppressed by expression of Activin and activated forms of the type I receptor ActRIB and Smad2. Expression of the murine EGF-CFC gene cripto rescues oep mutants. These results suggest a conserved role for EGF-CFC proteins as essential extracellular cofactors for Nodal signaling during vertebrate development.

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

“…5E-H vs. Q-T). This result is striking, because ventrolateral marginal expression of genes, such as no tail (ntl) and wnt11/silberblick, are not lost in MZoep mutants, even though there is a loss of all involuting mesendoderm (Gritsman et al, 1999). Importantly, dpr1 and dpr2 were still expressed in the ectoderm of MZoep embryos at 50 -60% epiboly stages (arrows in Fig.…”

“…To determine whether Nodal signaling is required to initiate their expression, I examined early dorsal dpr1 and dpr2 expression in maternal-zygotic one-eyed pinhead (MZoep) embryos, which lack all Nodal signaling due to a mutation in the required EGF-CFC coreceptor (Schier et al, 1997;Zhang et al, 1998;Gritsman et al, 1999). I found that early expression (at sphere stage) of dpr1 and dpr2 was the same in wild-type or MZoep embryos (Fig.…”

Loss of procollagen IIA from the anterior mesendoderm disrupts the development of mouse embryonic forebrain

“…In the zebrafish, NODAL-related protein activity in the prechordal mesoderm is implicated in direct regulation of Shh expression in the ventral forebrain (Sampath et al, 1998;Feldman et al, 1998;Gritsman et al, 1999). Although our results of the compound mutant study indicate that IIA and NODAL do not interact genetically in head development, there is striking resemblance of the pattern of gene expression in the forebrain of Smad2 CA/CA (the epiblast conditional mutant of Smad2), Nodal DPEE/413.d (a hypomorphic Nodal mutant; Vincent et al, 2003) and IIA À/À embryos.…”

Identification of nodal signaling targets by array analysis of induced complex probes

“…Of 115 enriched genes tested by in situ hybridization, 28.7% genes were expressed in the embryonic shield, the germ ring, and/or the yolk syncytial layer, the target tissues of Nodal signaling (Feldman et al, 1998a;Gritsman et al, 1999). As the zebrafish Nodals, Cyclops, and Squint are also expressed in these regions (Feldman et al, 1998a;Rebagliati et al, 1998;Sampath et al, 1998), these genes have a common expression domain with the Nodal ligands.…”