Expression of Wnt Signaling Components during Xenopus Pronephros Development

Zhang, Bo; Tran, Uyen; Wessely, Oliver

doi:10.1371/journal.pone.0026533

Cited by 31 publications

(27 citation statements)

References 63 publications

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“…This pathway involves G-proteins and, indeed, Ptx has been shown to perturb Wnt activity during tissue separation of the Xenopus gastrula (Winklbauer et al, 2001; Katanaev et al, 2005; Angers and Moon, 2009). Furthermore, several components of the non-canonical Wnt signaling pathway are expressed in the developing Xenopus pronephros (Zhang et al, 2011) and Frizzled-8 has been implicated in the morphogenetic processes regulating proximal tubular growth (Satow et al, 2004; Lienkamp et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Regulation of G-protein signaling via Gnas is required to regulate proximal tubular growth in the Xenopus pronephros

Zhang¹,

Romaker²,

Ferrell³

et al. 2013

Developmental Biology

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In the kidney, proximal tubules are very important for the reabsorption of water, ions and organic solutes from the primary urine. They are composed of highly specialized epithelial cells that are characterized by an elaborate apical brush border to increase transport efficiency. Using the pronephric kidney of Xenopus laevis we discovered that the G-protein modulator cholera toxin resulted in a dramatic reduction of the proximal tubular size. This phenotype was accompanied by changes in the cytoarchitecture characterized by ectopic expression of the distal tubular marker 4A6 and an impairment of yolk platelet degradation. In addition, cholera toxin caused edema formation. However, this phenotype was not due to kidney defects, but rather due to impaired vasculature development. Based on experiments with antisense morpholino oligomers as well as pharmacological agonists and antagonists, we could show that the complex phenotype of cholera toxin in the pronephric kidney was caused by the hyperactivation of a single G-protein alpha subunit, Gnas. This—in turn—caused elevated cAMP levels, triggered a Rapgef4-dependent signaling cassette and perturbed exo- and endocytosis. This perturbation of the secretory pathway by Ctx was not only observed in Xenopus embryos. Also, in a human proximal tubular cell line, cholera toxin or a Rapgef4-specific agonist increased uptake and decreased secretion of FITC-labeled Albumin. Based on these data we propose that the Gnas/cAMP/Rapgef4 pathway regulates the signals inducing the proliferation of proximal tubules to acquire their final organ size.

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Section: Discussionmentioning

confidence: 99%

Regulation of G-protein signaling via Gnas is required to regulate proximal tubular growth in the Xenopus pronephros

Zhang¹,

Romaker²,

Ferrell³

et al. 2013

Developmental Biology

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“…Celsr1-3 expression is also observed in other non-neural systems, such as the skin, lungs, heart, kidney, and spleen, as well as the digestive and reproductive systems ( Figure S4b-S4d) (Formstone et al 2000;Shima et al 2002;Yates et al 2010a,b;Zhang et al 2011). In the rodent testis, Celsr3 is expressed exclusively in post-mitotic germ cells, whereas Celsr1 and Celsr2 are expressed in Sertoli cells, with persistent post-natal down-regulation of Celsr1 and Celsr2 in adults ( Figure S4c) (Johnson et al 2000;Beall et al 2005).…”

Section: Tissue Distributionmentioning

confidence: 94%

“…,b; Zhang et al . ). In the rodent testis, Celsr3 is expressed exclusively in post‐mitotic germ cells, whereas Celsr1 and Celsr2 are expressed in Sertoli cells, with persistent post‐natal down‐regulation of Celsr1 and Celsr2 in adults (Figure S4c) (Johnson et al .…”

Section: Tissue Distributionmentioning

confidence: 97%

Understanding cadherin EGF LAG seven‐pass G‐type receptors

Wang

Zhang

et al. 2014

Journal of Neurochemistry

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The cadherin EGF LAG seven-pass G-type receptors (CELSRs) are a special subgroup of adhesion G protein-coupled receptors (GPCRs), which are pivotal regulators of many biological processes such as neuronal/endocrine cell differentiation, vessel valve formation and the control of planar cell polarity during embryonic development. All three members of the CELSR family (CELSR1-3) have large ecto-domains that form homophilic interactions and encompass more than 2,000 amino acids. Mutations in the ecto-domain or other gene locations of CELSRs are associated with neural tube defects (NTDs) and other diseases in humans. Celsr knockout (KO) animals have many developmental defects. Therefore, specific agonists or antagonists of CELSR members may have therapeutic potential. Although significant progress has been made regarding the functions and biochemical properties of CELSRs, our knowledge of these receptors is still lacking, especially considering that they are broadly distributed but have few characterized functions in a limited number of tissues. The dynamic activation and inactivation of CELSRs and the presence of endogenous ligands beyond homophilic interactions remain elusive, as do the regulatory mechanisms and downstream signaling of these receptors. Given this motivation, future studies with more advanced cell biology or biochemical tools, such as conditional KO mice, may provide further insights into the mechanisms underlying CELSR function, laying the foundation for the design of new CELSR-targeted therapeutic reagents.

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“…However, the evidence published to date suggests no compelling argument for the requirement of Ryk protein in the development of NCCs and their derivatives. Embryonic expression patterns of ryk genes in Xenopus and zebrafish show their strong enrichment in somite and central nervous system; expression is not enriched in dorsal neural tube at the times examined in this study, although ryk seems to be weakly and ubiquitously expressed in zebrafish at 19 hpf [73], [74]. Another Wnt receptor, Ror, is also a transmembrane tyrosine kinase, which contains Fzd-like cysteine-rich domain in the extracellular domain.…”

Section: Discussionmentioning

confidence: 62%

A Systematic Survey of Expression and Function of Zebrafish frizzled Genes

2013

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Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts) and receptors (Frizzleds) are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of frizzled (fzd) genes in zebrafish. To explore their functions, we focused on testing their requirement in several developmental events known to be regulated by Wnt signaling, convergent extension movements of gastrulation, neural crest induction, and melanocyte specification. We found fourteen distinct fzd genes in the zebrafish genome. Systematic analysis of their expression patterns between 1-somite and 30 hours post-fertilization revealed complex, dynamic and overlapping expression patterns. This analysis demonstrated that only fzd3a, fzd9b, and fzd10 are expressed in the dorsal neural tube at stages corresponding to the timing of melanocyte specification. Surprisingly, however, morpholino knockdown of these, alone or in combination, gave no indication of reduction of melanocytes, suggesting the important involvement of untested fzds or another type of Wnt receptor in this process. Likewise, we found only fzd7b and fzd10 expressed at the border of the neural plate at stages appropriate for neural crest induction. However, neural crest markers were not reduced by knockdown of these receptors. Instead, these morpholino knockdown studies showed that fzd7a and fzd7b work co-operatively to regulate convergent extension movement during gastrulation. Furthermore, we show that the two fzd7 genes function together with fzd10 to regulate epiboly movements and mesoderm differentiation.

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Expression of Wnt Signaling Components during Xenopus Pronephros Development

Cited by 31 publications

References 63 publications

Regulation of G-protein signaling via Gnas is required to regulate proximal tubular growth in the Xenopus pronephros

Regulation of G-protein signaling via Gnas is required to regulate proximal tubular growth in the Xenopus pronephros

Understanding cadherin EGF LAG seven‐pass G‐type receptors

A Systematic Survey of Expression and Function of Zebrafish frizzled Genes

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