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Nature 11/2007; 450(7167):E1-E2. · 36.28 Impact Factor
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ABSTRACT: Nodal signals induce mesodermal and endodermal progenitors during vertebrate development. To determine the role of Nodal signaling at a genomic level, we isolated Nodal-regulated genes by expression profiling using macroarrays and gene expression databases. Putative Nodal-regulated genes were validated by in situ hybridization screening in wild type and Nodal signaling mutants. 46 genes were identified, raising the currently known number of Nodal-regulated genes to 72. Based on their expression patterns along the dorsoventral axis, most of these genes can be classified into two groups. One group is expressed in the dorsal margin, whereas the other group is expressed throughout the margin. In addition to transcription factors and signaling components, the screens identified several new functional classes of Nodal-regulated genes, including cytoskeletal components and molecules involved in protein secretion or endoplasmic reticulum stress. We found that x-box binding protein-1 (xbp1) is a direct target of Nodal signaling and required for the terminal differentiation of the hatching gland, a specialized secretory organ whose specification is also dependent on Nodal signaling. These results indicate that Nodal signaling regulates not only specification genes but also differentiation genes.
Developmental Biology 05/2007; 304(2):525-40. · 4.07 Impact Factor
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ABSTRACT: Transcription factors belonging to the FoxH1 and Mixer families are required for facets of Nodal signaling during vertebrate mesendoderm induction. Here, we analyze whether zebrafish proteins related to FoxH1 [Schmalspur (Sur)] and Mixer [Bonnie and clyde (Bon)] act within or downstream of the Nodal signaling pathway, test whether these two factors have additive or overlapping activities, and determine whether FoxH1/Sur and Mixer/Bon can account for all Nodal signaling during embryogenesis. We find that sur expression is independent of Nodal signaling and that bon is expressed in the absence of Nodal signaling but requires Nodal signaling and Sur for enhanced, maintained expression. These results and the association of FoxH1 and Mixer/Bon with phosphorylated Smad2 support a role for these factors as components of the Nodal signaling pathway. In contrast to the relatively mild defects observed in single mutants, loss of both bon and sur results in a severe phenotype characterized by absence of prechordal plate, cardiac mesoderm, endoderm and ventral neuroectoderm. Analysis of Nodal-regulated proteins reveals that Bon and Sur have both distinct and overlapping regulatory roles. Some genes are regulated by both Bon and Sur, and others by either Bon or Sur. Complete loss of Nodal signaling results in a more severe phenotype than loss of both Bon and Sur, indicating that additional Smad-associated transcription factors remain to be identified that act as components of the Nodal signaling pathway.
Development 01/2004; 130(23):5589-99. · 6.60 Impact Factor
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ABSTRACT: The TGF-beta signals Nodal, Activin, GDF1, and Vg1 have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins, but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1 bind to and signal through Activin receptors only in the presence of EGF-CFC proteins. These results establish that multiple TGF-beta signals converge on Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for coreceptors in TGF-beta signaling than anticipated previously.
Genes & Development 02/2003; 17(1):31-6. · 11.66 Impact Factor
