Dataset Information

Induction of otic structures by canonical Wnt signalling in medaka.

ABSTRACT: The Wnt family of signalling proteins is known to participate in multiple developmental decisions during embryogenesis. We misexpressed Wnt1 in medaka embryos and observed anterior truncations, similar to those described for ectopic activation of canonical Wnt signalling in other species. Interestingly, when we induced a heat-shock Wnt1 transgenic line exactly at 30% epiboly, we observed multiple ectopic otic vesicles in the truncated embryos. The vesicles then fused, forming a single large ear structure. These "cyclopic ears" filled the complete anterior region of the embryos. The ectopic induction of otic development can be explained by the juxtaposition of hindbrain tissue with anterior ectoderm. Fibroblast growth factor (Fgf) ligands are thought to mediate the otic-inducing properties of the hindbrain. However, signals different from Fgf3 and Fgf8 are necessary to explain the formation of the ectopic ear structures, suggesting that Wnt signalling is involved in the otic induction process in medaka.

SUBMITTER: Bajoghli B

PROVIDER: S-EPMC2773112 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Induction of otic structures by canonical Wnt signalling in medaka.

Bajoghli Baubak B Bajoghli Baubak B Aghaallaei Narges N Jung Gerlinde G Czerny Thomas T

Development genes and evolution 20090801 8

The Wnt family of signalling proteins is known to participate in multiple developmental decisions during embryogenesis. We misexpressed Wnt1 in medaka embryos and observed anterior truncations, similar to those described for ectopic activation of canonical Wnt signalling in other species. Interestingly, when we induced a heat-shock Wnt1 transgenic line exactly at 30% epiboly, we observed multiple ectopic otic vesicles in the truncated embryos. The vesicles then fused, forming a single large ear ...[more]

PMID: 19760182

Similar Datasets

Project description:Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing ?-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic ?-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.

Project description:Several studies have provided compelling evidence implicating the Wnt signalling pathway in the pathogenesis of diabetic nephropathy. Gene expression profiles associated with renal fibrosis have been attenuated through Wnt pathway modulation in model systems implicating Wnt pathway members as potential therapeutic targets for the treatment of diabetic nephropathy. We assessed tag and potentially functional single nucleotide polymorphisms (SNPs; n?=?31) in four key Wnt pathway genes (CTNNB1, AXIN2, LRP5 and LRP6) for association with diabetic nephropathy using a case-control design.SNPs were genotyped using Sequenom or Taqman technologies in 1351 individuals with type 1 diabetes (651 cases with nephropathy and 700 controls without nephropathy). Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Adjustment for multiple testing was performed by permutation testing.Following logistic regression analysis adjusted by collection centre, duration of T1D, and average HbA1c as covariates, a single SNP in LRP6 (rs1337791) was significantly associated with DN (OR?=?0.74; CI: 0.57-0.97; P?=?0.028), although this was not maintained following correction for multiple testing. Three additional SNPs (rs2075241 in LRP6; rs3736228 and rs491347 both in LRP5) were marginally associated with diabetic nephropathy, but none of the associations were replicated in an independent dataset. Haplotype and subgroup analysis (according to duration of diabetes, and end-stage renal disease) also failed to reveal an association with diabetic nephropathy.Our results suggest that analysed common variants in CTNNB1, AXIN2, LRP5 and LRP6 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes or other members of the Wnt pathway, from involvement in the pathogenesis of diabetic nephropathy as our study had limited power to detect variants with small effect size.

Dataset Information

Induction of otic structures by canonical Wnt signalling in medaka.

Publications

Induction of otic structures by canonical Wnt signalling in medaka.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets