fast1 is required for the development of dorsal axial structures in zebrafish

Sirotkin, Howard I.; Gates, Michael A.; Kelly, Peter D.; Schier, Alexander F.; Talbot, William S.

doi:10.1016/s0960-9822(00)00679-5

Cited by 103 publications

(51 citation statements)

References 31 publications

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“…Single Smad2 knockdown resulted in a curved, shortened body axis, anterior truncation, and loss of floorplate (see Fig. S5 in the supplementary material), reminiscent of mutant sur (Pogoda et al, 2000;Sirotkin et al, 2000) and similar to the phenotype described for Smad2 knockdown in Xenopus (Rana et al, 2006).…”

Section: Research Articlesupporting

confidence: 57%

Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination

et al. 2007

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During vertebrate development, signaling by the TGF␤ ligand Nodal is critical for mesoderm formation, correct positioning of the anterior-posterior axis, normal anterior and midline patterning, and left-right asymmetric development of the heart and viscera. Stimulation of Alk4/EGF-CFC receptor complexes by Nodal activates Smad2/3, leading to left-sided expression of target genes that promote asymmetric placement of certain internal organs. We identified Ttrap as a novel Alk4-and Smad3-interacting protein that controls gastrulation movements and left-right axis determination in zebrafish. Morpholino-mediated Ttrap knockdown increases Smad3 activity, leading to ectopic expression of snail1a and apparent repression of e-cadherin, thereby perturbing cell movements during convergent extension, epiboly and node formation. Thus, although the role of Smad proteins in mediating Nodal signaling is well-documented, the functional characterization of Ttrap provides insight into a novel Smad partner that plays an essential role in the fine-tuning of this signal transduction cascade.

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Section: Research Articlesupporting

confidence: 57%

Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination

et al. 2007

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“…Consistent with this line of reasoning, introduction of lefty to tumor cells reduces tumor growth in nude mice. 2 The lefty protein is expressed as a precursor of 42 kDa that is cleaved at Arg 77 and Arg 135 to release polypeptides of 34 and 28 kDa, respectively (71). We found the 28-kDa lefty polypeptide to induce MAPK activity, but the 34-kDa protein appears to be inactive.…”

mentioning

confidence: 75%

“…The transcription factor FAST2, which mediates signaling by TGF-␤ and activin, binds to a conserved sequence in this asymmetric enhancer, which is both essential and sufficient for left/right asymmetric gene expression (73,74). The forkhead transcription factor FoxH1, also known as FAST1, which associates with Smad proteins in response to an activin/TGF-␤ signal, plays a key role in the development of dorsal axial structures in zebrafish and in specification of mesoderm by TGF-␤ superfamily signals during early Xenopus embryogenesis (75)(76)(77). These findings directly tie the lefty functions to the action of TGF-␤ and its signaling molecules during embryogenesis.…”

mentioning

confidence: 99%

Lefty Inhibits Receptor-regulated Smad Phosphorylation Induced by the Activated Transforming Growth Factor-β Receptor

Ulloa

Tabibzadeh

2001

Journal of Biological Chemistry

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Transforming growth factor-␤ (TGF-␤ TGF-␤1 is a potent and pleiotropic cytokine that regulates cell growth and differentiation, embryonic patterning, deposition of the extracellular matrix, and fibrosis (1-7). To exert these functions, TGF-␤ brings together two transmembrane serine/threonine kinases, the type I and II receptors. The assembly and oligomerization of TGF-␤ receptors lead to phosphorylation of receptor-regulated Smad (R-Smad) proteins, heterodimerization of R-Smad proteins with Smad4, and subsequent nuclear accumulation of these complexes (8 -11). Activated Smad complexes interact with other transcription factors in the nucleus (12-15), bind to DNA by their N-terminal Mad homology-1 domains (16 -21), and activate transcription of TGF-␤-responsive genes through the C-terminal Mad homology-2 domains (1, 3, 4).In view of its diverse and potent activities, the signaling by TGF-␤ is under tight regulation both by positive and negative feedback mechanisms. The two principal events in TGF-␤ signaling, TGF-␤ receptor and Smad phosphorylation, are controlled by a network of regulatory proteins, which modulate the magnitude of signals induced by TGF-␤ (22). Positive regulators include ligand accessory receptors and substrate-anchoring factors such as membrane-anchored proteoglycan, betaglycan, and SARA (Smad anchor for receptor activation). Betaglycan, also known as the TGF-␤ type III receptor, binds TGF-␤ and increases its affinity for the signaling receptors (23,24). By binding to the Mad homology-2 domains of Smad2 and Smad3, SARA facilitates the interaction of these Smad proteins with TGF-␤ receptors (25). A second set of factors participating in the negative regulation of TGF-␤ signaling includes the cytosolic growth factor-sequestering protein FKBP-12, the pseudoreceptor transmembrane protein BAMBI, and a set of inhibitory Smad proteins that include Smad6 and Smad7. Some of these factors inhibit the function of TGF-␤ by interacting with TGF-␤ receptors or Smad proteins. By virtue of binding to TGF-␤ type I receptor, FKBP-12 prevents its transphosphorylation by the TGF-␤ type II receptor (26). BAMBI, on the other hand, blocks TGF-␤-mediated signaling by forming inactive dimers with the type I receptor (27). By binding to receptor-activated Smad1, Smad6 forms a Smad1⅐Smad6 complex, which appears to be inactive (28), whereas a second inhibitory Smad protein, Smad7, binds to the activated TGF-␤ receptor, blocking the phosphorylation of receptor-regulated Smad (34,35). Among the intracellular transcriptional repressors thus far identified that block TGF-␤ signaling are two closely related members of the Ski/sno family of nuclear oncoproteins, . Ski was identified on the basis of homology to v-Ski, the transforming protein of the Sloan-Kettering virus. SnoN and c-Ski both inhibit TGF-␤ signaling by interfering with Smad function (36). TGF-␤-mediated Smad signaling integrates with and is controlled by other signaling factors such as those in the Ras/Erk and Jak1/Stat pathways (37, 38). Erk, activated by growth...

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“…Interestingly, mutations in 3 genes, aku, ake and moc of Class 1D result in a phenotype similar to that of one-eyed-pinhead (oep) in zebrafish (Schier et al, 1997;Strahle et al, 1997). In zebrafish, mutants of other genes involved in Nodal signaling, cyclops(cyc), squint (sqt), and schmalspur (sur) displayed slightly different phenotypes, suggesting a divergence of the molecular components in a signaling pathway between the two species (Hatta et al, 1994;Brand et al, 1996b;Malicki et al, 1996;Schier et al, 1996;Heisenberg and Nusslein-Volhard, 1997;Feldman et al, 1998;Rebagliati et al, 1998;Sampath et al, 1998;Pogoda et al, 2000;Sirotkin et al, 2000). Similarly, mutations in 3 genes, oob, sam, and sgu, caused phenotypes that are reminiscent of those of parachute zebrafish mutant of the N-cadherin gene.…”

Section: Medaka and Zebrafish Complement To Genetically Dissect Forebmentioning

confidence: 95%

Genetic dissection of the formation of the forebrain in Medaka, Oryzias latipes

Kitagawa

Watanabe

Saito

et al. 2004

Mechanisms of Development

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The forebrain, consisting of the telencephalon and diencephalon, is essential for processing sensory information. To genetically dissect formation of the forebrain in vertebrates, we carried out a systematic screen for mutations affecting morphogenesis of the forebrain in Medaka. Thirty-three mutations defining 25 genes affecting the morphological development of the forebrain were grouped into two classes. Class 1 mutants commonly showing a decrease in forebrain size, were further divided into subclasses 1A to 1D. Class 1A mutation (1 gene) caused an early defect evidenced by the lack of bf1 expression, Class 1B mutations (6 genes) patterning defects revealed by the aberrant expression of regional marker genes, Class 1C mutation (1 gene) a defect in a later stage, and Class 1D (3 genes) a midline defect analogous to the zebrafish one-eyed pinhead mutation. Class 2 mutations caused morphological abnormalities in the forebrain without considerably affecting its size, Class 2A mutations (6 genes) caused abnormalities in the development of the ventricle, Class 2B mutations (2 genes) severely affected the anterior commissure, and Class 2C (6 genes) mutations resulted in a unique forebrain morphology. Many of these mutants showed the compromised sonic hedgehog expression in the zona-limitans-intrathalamica (zli), arguing for the importance of this structure as a secondary signaling center. These mutants should provide important clues to the elucidation of the molecular mechanisms underlying forebrain development, and shed new light on phylogenically conserved and divergent functions in the developmental process.

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fast1 is required for the development of dorsal axial structures in zebrafish

Cited by 103 publications

References 31 publications

Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination

Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination

Lefty Inhibits Receptor-regulated Smad Phosphorylation Induced by the Activated Transforming Growth Factor-β Receptor

Genetic dissection of the formation of the forebrain in Medaka, Oryzias latipes

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