The nieuwkoid gene characterizes and mediates a Nieuwkoop-center-like activity in the zebrafish

Koos, David S.; Ho, Ruoya

doi:10.1016/s0960-9822(07)00509-x

Cited by 72 publications

(67 citation statements)

References 35 publications

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“…2E). A loss of posterior structures also occurs in dorsalized embryos, as caused by the loss of Bmp signaling (Mullins, 1999) or by overexpression of boz (Yamanaka et al, 1998;Koos and Ho, 1998). Like in embryos injected with boz mRNA, but unlike in bmp mutants, admp morphant embryos display a significant enlargement of the organizer (Fig.…”

Section: Resultsmentioning

confidence: 94%

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

Lele

Nowak

Hammerschmidt

2001

Developmental Dynamics

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Bone morphogenetic proteins (Bmps) and their roles during early dorsoventral patterning of the vertebrate embryo are well understood. The role and regulation of a more distant member of this family, the anti-dorsalizing morphogenetic protein (Admp), however, are less clear. Here, we report the isolation and characterization of zebrafish admp. Unlike other bmps, admp is exclusively expressed on the dorsal side. Expression starts at blastula stages in the region of the organizer, giving rise to anterior neuroectoderm and axial mesoderm. During the course of gastrulation, both the neuroectodermal and the mesodermal admp transcripts vanish in an anterior-posterior wave. The maintenance of admp expression is positively influenced by Nodal signaling and by Bozozok (Boz), an organizer-promoting homeodomain protein acting as a repressor of early bmp2b expression. Despite the positive effect of boz on admp expression, Boz and Admp have rather opposite effects on zebrafish patterning, as revealed in gain-and loss-of-function experiments. Upon overexpression, admp has Bmp-like activities causing a smaller organizer and enhanced ventral specification, very similar to the phenotype caused by the loss of boz function in mutant embryos. Antisense-based admp knockdown, on the other side, leads to an enlarged organizer and impaired ventral and posterior development, as observed in embryos after boz overexpression. This finding indicates that admp is required for the development of embryonic structures normally suppressed by organizer activities. The seeming discrepancy between the regulative and functional relationship of boz and admp is discussed, and models are proposed according to which Admp might be part of a negative feedback loop to pattern and confine the organizer region.

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Section: Resultsmentioning

confidence: 94%

“…In contrast to Nodals and Admp, Boz promotes and is required for head formation (Yamanaka et al, 1998;Koos and Ho, 1998;Fekany et al, 1999;Koos and Ho, 1999). Nevertheless, boz and mzoep mutants display a very similar admp expression pattern.…”

Section: Resultsmentioning

confidence: 99%

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

Lele

Nowak

Hammerschmidt

2001

Developmental Dynamics

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“…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). Taken together, available data establish a key role for Wnt signaling and its early targets in early dorsoventral axis specification (Moon and Kimelman 1998;Schroeder et al 1999;Sokol 1999;Tao et al 2005).…”

Section: Role Of Cytoplasmic Determinants and Wnt Signaling In Dorsovmentioning

confidence: 99%

“…1997;Fan etal. 1998) and Twin (Laurent et al 1997), zebrafish Bozozok/dharma/nieuwkoid (Koos and Ho 1998;Yamanaka et al 1998;Fekany et al 1999), Xnr3 (Smith et al 1995), Xnr5/6 (Takahashi et al 2000;Yang et al 2002) and several Wnt antagonists: Frzb/Sfrp3 (Leyns et al 1997), Dkk1 (Glinka et al 1998), Crescent (Shibata et al 2000), Cerberus (Bouwmeester et al 1996), Shisa (Yamamoto et al 2005), as well as other genes listed in Table 2. The difference between the early and late targets for the Wnt pathway corresponds to the switch between stage-specific Wnt signaling mechanisms that are critical for vertebrate axis specification.…”

Section: Putative Transcriptional Targets Of the Wnt Pathway In Axis mentioning

confidence: 99%

Wnt Signaling in Vertebrate Axis Specification

Hikasa

Sokol

2012

Cold Spring Harbor Perspectives in Biology

162

165

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“…boz mutant embryos lack axial mesoderm and have severe patterning defects in the anterior neuroectoderm (Solnica-Krezel et al, 1996;Solnica-Krezel and Driever, 2001). boz encodes a homeodomain protein also known as Dharma and Nieuwkoid (Koos and Ho, 1998;Yamanaka et al, 1998;Fekany et al, 1999). It is transcribed in dorsal blastomeres and in the dorsal yolk syncytial layer from the earliest zygotic gene expression until early gastrula (Yamanaka et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

bozozokdirectly repressesbmp2btranscription and mediates the earliest dorsoventral asymmetry ofbmp2bexpression in zebrafish

et al. 2003

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Formation of the gastrula organizer requires suppression of ventralizing signals and, in fish and frog, the need to counteract the effect of ubiquitously present maternal factors that activate the expression of Bmps. How the balance between dorsalizing and ventralizing factors is shifted towards organizer establishment at late blastula stages is not well understood. Mutations in zebrafish bozozok (boz) cause severe defects in axial mesoderm and anterior neurectoderm and affect organizer formation. The boz gene encodes the homeodomain protein Bozozok/ Dharma and its expression in the region of the organizer is activated through β-catenin signaling. Here, we investigate the molecular mechanism by which boz contributes to the establishment of the organizer. We demonstrate that the homeodomain protein Boz acts as a transcriptional repressor in zebrafish: overexpression of an En-Boz fusion protein can rescue the boz phenotype, whereas a VP16-Boz fusion protein acts as an antimorph. Expression analysis of bmp2b indicates that Boz negatively regulates bmp2b in the prospective organizer. We demonstrate that this Boz activity is independent of that of other zygotic genes, because it also occurs when translation of zygotic genes is suppressed by cycloheximide (CHX). We identify two highaffinity binding sites for Boz within the first intron of the bmp2b gene. Deletion of these control elements abolishes Boz-dependent repression of bmp2b in the early blastula. Thus, Boz directly represses bmp2b by binding to control elements in the bmp2b locus. We propose that early transcriptional repression of bmp2b by Boz is one of the first steps toward formation of a stable organizer, whereas the later-acting Bmp antagonists (e.g. Chordin, Noggin) modulate Bmp activity in the gastrula to induce patterning along the dorsoventral axis. Thus, similar to Drosophila Dpp, asymmetry of Bmp expression in zebrafish is initiated at the transcriptional level, and the shape of the gradient and its function as a morphogen are later modulated by post-transcriptional mechanisms.

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The nieuwkoid gene characterizes and mediates a Nieuwkoop-center-like activity in the zebrafish

Cited by 72 publications

References 35 publications

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

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

Wnt Signaling in Vertebrate Axis Specification

bozozokdirectly repressesbmp2btranscription and mediates the earliest dorsoventral asymmetry ofbmp2bexpression in zebrafish

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