Two different vestigial like 4 genes are differentially expressed during Xenopus laevis development

Barrionuevo, M.; Aybar, Manuel J.; Tríbulo, Celeste

doi:10.1387/ijdb.130353ct

Cited by 12 publications

(7 citation statements)

References 21 publications

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“…Tgi and VGLL4 contain two conserved Tondu domains responsible for the interaction with Sd and TEAD transcription factors, respectively ( Figure 1B) (GUO et al 2013;KOONTZ et al 2013). In addition, as reported previously (BARRIONUEVO et al 2014), we observed three conserved regions in Tgi: the N terminal region, and two short motifs between this region and the first Tondu domain ( Figure 1B). The first short conserved Tgi motif (PIDMS) bears strong resemblance to a consensus CtBP-interaction motif (PxDLS, where x is any amino acid) ( Figure 1C).…”

Section: Tgi Forms a Physical Complex With Pits And Ctbp Via Conservesupporting

confidence: 89%

Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi

Vissers

House

Kondo

et al. 2019

Preprint

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The Hippo pathway is an evolutionary conserved signalling network that regulates organ size, cell fate control and tumorigenesis. In the context of organ size control, the pathway incorporates a large variety of cellular cues such as cell polarity and adhesion into an integrated transcriptional response.The central Hippo signalling effector is the transcriptional co-activator Yorkie, which controls gene expression in partnership with different transcription factors, most notably Scalloped. When it is not activated by Yorkie, Scalloped can act as a repressor of transcription, at least in part due to its interaction with the corepressor protein Tgi. The mechanism by which Tgi represses transcription is incompletely understood and therefore we sought to identify proteins that potentially operate together with it. Using an affinity purification and mass-spectrometry approach we identified Pits and CtBP as Tgi-interacting proteins, both of which have been linked to transcriptional repression.Both Pits and CtBP were required for Tgi to suppress the growth of the D. melanogaster eye and CtBP loss suppressed the undergrowth of yorkie mutant eye tissue. Furthermore, as reported previously for Tgi, overexpression of Pits suppressed transcription of Hippo pathway target genes.These findings suggest that Tgi might operate together with Pits and CtBP to repress transcription of genes that normally promote tissue growth. The human orthologues of Tgi, CtBP and Pits (VGLL4, CTBP2 and IRF2BP2) physically and functionally interact to control transcription, implying that the mechanism by which these proteins control transcriptional repression is conserved throughout evolution.

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Section: Tgi Forms a Physical Complex With Pits And Ctbp Via Conservesupporting

confidence: 89%

Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi

Vissers

House

Kondo

et al. 2019

Preprint

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“…The VGLL4 TDU domains form bridges to interact with proteins such as TEAD1(26), IRF2BP2 [64] and Myocyte Enhancer Factor 2 (MEF2) [65]. Therefore, we injected Irf2bp2a , irf2bp2b , tead1a , tead3b , mef2ca and mef2cb mRNAs into zebrafish embryos.…”

Section: Resultsmentioning

confidence: 99%

The NOTCH1-dependent HIF1α/VGLL4/IRF2BP2 oxygen sensing pathway triggers erythropoiesis terminal differentiation

et al. 2020

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Hypoxia is widely considered as a limiting factor in vertebrate embryonic development, which requires adequate oxygen delivery for efficient energy metabolism, while nowadays some researches have revealed that hypoxia can induce stem cells so as to improve embryonic development. Erythroid differentiation is the oxygen delivery method employed by vertebrates at the very early step of embryo development, however, the mechanism how erythroid progenitor cell was triggered into mature erythrocyte is still not clear. In this study, after detecting the upregulation of vgll4b in response to oxygen levels, we generated vgll4b mutant zebrafish using CRISPR/Cas9, and verified the resulting impaired heme and dysfunctional erythroid terminal differentiation phenotype. Neither the vgll4b-deficient nor the γ-secretase inhibitor IX (DAPT)-adapted zebrafish were able to mediate HIF1α-induced heme generation. In addition, we showed that vgll4b mutant zebrafish were associated with an impaired erythroid phenotype, induced by the downregulation of alas2, which could be rescued by irf2bp2 depletion. Further mechanistic studies revealed that zebrafish VGLL4 sequesters IRF2BP2, thereby inhibiting its repression of alas2 expression and heme biosynthesis. These processes occur primarily via the VGLL4 TDU1 and IRF2BP2 ring finger domains. Our study also indicates that VGLL4 is a key player in the mediation of NOTCH1-dependent HIF1α-regulated erythropoiesis and can be sensitively regulated by oxygen concentrations. On the other hand, VGLL4 is a pivotal regulator of heme biosynthesis and erythroid terminal differentiation, which collectively improve oxygen metabolism.

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“…VGLL4 (MIM# 6186962) encodes vestigial-like family member 4 (Supplementary Table S6 and Figures 8-11). Studies in zebrafish (Xue et al, 2018), xenopus (Barrionuevo et al, 2014;Faucheux et al, 2010) and mice suggested that VGLL4 takes part in early embryonic development, including eye development. Interestingly, this gene is a part of the Hippo signaling pathway, which has also been implicated in myopia (Zhu et al, 2018).…”

Section: Bdnf (Mim# 113505) Encoding Brain-derived Neurotrophic Facto...mentioning

confidence: 99%

Shedding light on myopia by studying complete congenital stationary night blindness

Zeitz¹,

Roger²,

Michiels³

et al. 2022

Acta Ophthalmologica

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Purpose: Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signalling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON‐bipolar cell signal transmission defect and is also associated with high myopia. The purpose of this work was to identify the molecular cause of myopia present in cCSNB. Methods: A whole transcriptome sequencing (RNA‐seq) approach was performed using retina from three mouse lines with cCSNB, Gpr179−/−, Lrit3−/− and Grm6−/− and the expression data compared to data of age‐matched wild‐type littermates (n = 5). DEGs with fold changes of at least 1.2, p‐values of ≤0.01, an expression value of at least 5 transcripts per million reads and appearing in at least two cCSNB mouse lines were investigated in detail. A meta‐analysis was performed by (a) comparing our data with published transcriptome data from purified retinal cells and single cell RNA‐Seq data, (b) pathway analyses, (c) myopia databases and publications concerning their role in normal vision. Several of the DEGs were validated by RT‐qPCR experiments and analysed by western blot and immunolocalization studies. Results: More than 50 DEGs were found in at least two cCSNB mouse lines. Expression of those was found in different retinal cell types. The difference in expression was independent of the number of nuclei present in wild‐type and mutant inner retina. Pathway analysis revealed that mitogen‐activated protein kinase pathways, synaptic signalling, G protein‐coupled receptor ligand binding pathways, and proteins implicated in eye, endoderm and connective tissue development were affected in cCSNB. More than half of the genes were already associated with myopia. Conclusions: Our study reveals DEGs in all retinal cell types of cCSNB models, previously associated with myopia and novel candidates. These studies combined with pathway analyses provide the basis for the development of pharmacological and optical myopia therapies.

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Two different vestigial like 4 genes are differentially expressed during Xenopus laevis development

Cited by 12 publications

References 21 publications

Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi

Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi

The NOTCH1-dependent HIF1α/VGLL4/IRF2BP2 oxygen sensing pathway triggers erythropoiesis terminal differentiation

Shedding light on myopia by studying complete congenital stationary night blindness

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