Zebrafish
            <i>GADD45</i>
            β genes are involved in somite segmentation

Kawahara, Atsuo; Che, Yong-Suk; Hanaoka, Ryuki; Takeda, Hiroyuki; Dawid, Igor B.

doi:10.1073/pnas.0408726102

Cited by 26 publications

(22 citation statements)

References 31 publications

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“…Gadd45 proteins are involved in cell-cycle regulation and are normally induced by genome damage and stress conditions, and regulate somite formation in zebrafish. 51 The gadd45al, gadd45bl and gadd45b genes were upregulated 2.6, 2.3 and 2.6 in embryos expressing the Ser-tRNA CAC Val and 2.1, 2.5 and 2.4 in embryos expressing the Ser-tRNA CAG Leu , supporting the hypothesis that mistranslation affects the genome stability.…”

Section: Global Transcriptional Responses To Proteome Instability Indsupporting

confidence: 60%

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

et al. 2014

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Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability.

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Section: Global Transcriptional Responses To Proteome Instability Indsupporting

confidence: 60%

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

et al. 2014

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“…At 8-ss, the expression of panendothelial fli-1, together with that of notochord no-tail 24 and of nascent somite myoD, 25 were not affected in crlr morphants, thus indicating the lack of alterations in the vascular and nonvascular differentiation programs prior to this time of development ( Figure S2). In keeping with the data obtained with tg(fli1:EGFP) y1 embryos, the fli-1 transcript was abundantly expressed in the axial vasculature of both control and crlr morphants at 28 hpf, indicating that endothelial cell migration and localization is not defective in the embryos lacking crlr activity.…”

Section: Mo Knockdown Of Crlr Function Results In Vascular Defectsmentioning

confidence: 90%

Calcitonin receptor-like receptor guides arterial differentiation in zebrafish

Nicoli

Tobia

Gualandi

et al. 2008

Blood

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The calcitonin receptor-like receptor (crlr) is a major endothelial cell receptor for adrenomedullin, a peptide vasodilator involved in cardiovascular development, homeostasis, and disease. Here, we used the zebrafish (Danio rerio) model to characterize the role of crlr in vascular development. Crlr is expressed within somites from the 4-to the 13-somite stage and by arterial progenitors and axial vessels during zebrafish development. Loss of crlr results in profound alterations in vascular development and angiogenesis, including atrophic trunk dorsal aorta and interruption of anterior aortic bifurcation, delay in intersomitic vessel development, and lack of blood circulation. Remarkably, crlr morphants are characterized by the loss of arterial endothelial cell identity in dorsal aorta, as shown by the lack of expression of the arterial markers ephrin-B2a, DeltaC, and notch5. Down-regulation of crlr affects vascular endothelial growth factor (vegf) expression, whereas vegf overexpression is sufficient to rescue arterial differentiation in crlr morphants. Finally, genetic and biochemical evidences indicate that somitic crlr expression is under the control of sonic hedgehog. These data demonstrate that crlr plays a nonredundant role in arterial differentiation, representing a novel element of the sonic hedgehog- vegf IntroductionThe calcitonin receptor-like receptor (crlr) is a promiscuous 7-transmembrane G protein-coupled receptor (GPCR) that binds various ligands by forming complexes with different receptor activity-modifying proteins (RAMPs). 1 The interaction of crlr protein with RAMP-2 or RAMP-3 leads to the formation of heterodimeric complexes representing the functional receptors for adrenomedullin, a peptide vasodilator involved in cadiovascular stresses and tumor angiogenesis. 2 crlr is highly expressed in endothelium, 3 and crlr-null mice die in utero at midgestation with hydrops fetalis and developmental abnormalities in cardiovascular tissues. 4 Remarkably, adrenomedullin-null mice show a similar cardiovascular phenotype that provides compelling genetic and in vivo evidence that crlr is the primary receptor through which adrenomedullin acts during embryonic development. 4 In vertebrates, the large midline artery and vein are the first blood vessels to develop via a vasculogenic process that involves migration, differentiation, and assembly of the vascular endothelial growth factor (vegf) receptor-2 (kdr) ϩ angioblasts from the lateral posterior mesoderm. 5 Molecular differences exist between arterial and venous endothelial cells before the onset of circulation and the activation of complex genetic pathways specifies artery and vein identity, leading to the expression of specific arterial and venous markers (eg, ephrin-B2a and ephB4, respectively). 6 Genetic alterations of arterial/venous specification are hypothesized to be responsible for congenital hereditary arteriopathies. Indeed, mutations of notch pathway components involved in arterial specification are associated with congenital defects of the...

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“…doi:10.1016/j.mod.2011.08.002 obvious malformations (Hoffmeyer et al, 2001). In zebrafish two Gadd45b homologs have been identified which are expressed periodically in the anterior presomitic mesoderm, where they regulate somitogenesis (Kawahara et al, 2005). Furthermore, Gadd45a may be involved in neural development, possibly by promoting DNA demethylation of pro-neural genes (Rai et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

Gadd45a and Gadd45g regulate neural development and exit from pluripotency in Xenopus

Kaufmann

Niehrs

2011

Mechanisms of Development

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Gadd45 genes encode a small family of multifunctional stress response proteins, mediating cell proliferation, apoptosis, DNA repair and DNA demethylation. Their role during embryonic development is incompletely understood. Here we identified Xenopus Gadd45b, compared Gadd45a, Gadd45b and Gadd45g expression during Xenopus embryogenesis, and characterized their gain and loss of function phenotypes. Gadd45a and Gadd45g act redundantly and double Morpholino knock down leads to pleiotropic phenotypes, including shortened axes, head defects and misgastrulation. In contrast, Gadd45b, which is expressed at very low levels, shows little effect upon knock down or overexpression. Gadd45ag double Morphants show reduced neural cell proliferation and downregulation of pan-neural and neural crest markers. In contrast, Gadd45ag Morphants display increased expression of multipotency marker genes including Xenopus oct4 homologs as well as gastrula markers, while mesodermal markers are downregulated. The results indicate that Gadd45ag are required for early embryonic cells to exit pluripotency and enter differentiation.

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Zebrafish GADD45 β genes are involved in somite segmentation

Cited by 26 publications

References 31 publications

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

Calcitonin receptor-like receptor guides arterial differentiation in zebrafish

Gadd45a and Gadd45g regulate neural development and exit from pluripotency in Xenopus

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