Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA591581 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10528563.fastq.gz | Fastqsanger.gz | |||
| SRR10528564.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3’-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.
2021-05-01 | GSE140931 | GEO
Project description: Not available
| S-EPMC8249388 | biostudies-literature
Project description:Structural birth defects are the leading cause of infant mortality in the United States. Many of these defects are associated with abnormal anatomical left-right asymmetry. Despite the importance of orienting organs along the left-right (L-R) axis during development, very little is known about the molecular events that control this process. To elucidate the genetic mechanisms that shape the L-R asymmetry of individual organs, we sought to identify genes that are expressed in L-R asymmetric patterns during organ development. To accomplish this goal, we took advantage of the exceptionally large Budgett’s frog (Lepidobatrachus laevis) embryo to profile gene expression by RNA-seq in the left versus right halves of the developing stomach. Using this data, we have constructed a de novo Lepidobatrachus transcriptome and identified ~26,000 unique transcripts with human homology based on reciprocal BLAST analyses. Over 300 transcripts were L-R asymmetrically expressed within the stomach. Among these candidates are some of the few genes already known to play a role in L-R asymmetric development, validating our strategy for L-R gene discovery.
2023-05-26 | GSE99817 | GEO
Project description:We recently identified Bicc1 as a regulator of osteoblast differentiation and bone mass. Bicc1 encodes an RNA-binding protein. Here, we have used siRNA to decrease Bicc1 expression in primary calvarial osteoblasts. Illlumina microarrays were then used to profile global gene expression changes.
2014-03-25 | GSE51693 | GEO
Project description:Autosomal dominant polycystic kidney disease (ADPKD) is primarily of adult-onset and caused by pathogenic variants in PKD1 or PKD2. Variable disease expression is incompletely understood with rare very early-onset PKD (VEO-PKD) presentations in utero or infancy. In animal models, the RNA-binding molecule Bicc1 has been shown to play a crucial role in the pathogenesis of PKD. To further investigate this, we first demonstrated that BICC1 physically binds to the proteins Polycystin-1 and -2 encoded by PKD1 and PKD2 via distinct protein domains. Furthermore, PKD was aggravated in loss-of-function studies in Xenopus and mice. These resulted in more severe disease when Bicc1 was depleted in conjunction with Pkd1, Pkd2 or Pkhd1., Finally, in a large human patient cohort, we identified several VEO-PKD patients that exhibited compound situations of PKD1, PKD2 and PKHD1 in conjunction with BICC1 as well as a sibling pair with a homozygous BICC1 mutation. Together these findings support the hypothesis that BICC1 cooperates with PKD1 and PKD2, and that BICC1 variants may aggravate disease severity highlighting RNA metabolism as an important new concept for disease modification in ADPKD.
2025-06-28 | GSE262417 | GEO
Project description:We recently identified Bicc1 as a regulator of osteoblast differentiation and bone mass. Bicc1 encodes an RNA-binding protein. Here, we have used siRNA to decrease Bicc1 expression in primary calvarial osteoblasts. Illlumina microarrays were then used to profile global gene expression changes. The experiment consisted of 16 total samples in 4 treatment groups (N=4 replicates per treatment). The treatment groups were osteoblasts treated with 1). control scrambled siRNA, 2) Bicc1_1 siRNA, 3) Bicc1_2 siRNA and 3) Bicc1_3 siRNA. Cells were isolated, transfected and 48 hours later RNA was isolated and hybridized to arrays.
2014-03-25 | E-GEOD-51693 | biostudies-arrayexpress
Project description:Mutations in Bicaudaul C 1 (BICC1), evolutionary conserved RNA-binding protein, cause renal cysts in mice and humans. These renal cysts are reminiscent of Polycystic Kidney Disease (PKD). How BICC1 is involved in the pathogenesis of polycystic kidney disease is still unknown. Recent studies highlighted that HNF4A plays a role in the regulation of metabolic pathways deregulated in this renal disease. Moreover, Menezes et al. [2012, https://doi.org/10.1371/journal.pgen.1003053] showed that combined kidney inactivation of Hnf4a and Pkd1 in mice significantly worsened the cystic phenotype. Here we investigated whether the DNA binding and transcriptional activity of HNF4A might be deregulated in kidneys from Bicc1 mouse model of polycystic kidney disease. HNF4A, H3K27ac, H3K4me1 ChIPseq experiments were performed in kidneys from male and female Bicc1 WT and KO mice. From the contralateral kidneys of the same animals used for the ChIPseq experiments, the total RNA was extracted for gene expression profiling by RNAseq. The RNAseq data was used to support the ChIP-seq analysis and to reveal deregulated pathways in BICC1 mutants.
2020-01-20 | E-MTAB-6423 | biostudies-arrayexpress
Project description:Colonic Crohn's left and right colon
| PRJNA593867 | ENA
Project description:Asymmetrical gonadal development is an intriguing phenomenon observed in the majority of female birds. In chickens, the left gonad of female embryos develops into a functional ovary, while the right gonad undergoes degeneration during embryogenesis. This sexually dimorphic trait is primarily induced by the spatial differential expression of the PITX2 gene. However, a comprehensive understanding of the transcriptional profile of the developing gonads during asymmetric development is still lacking. To elucidate the molecular mechanism of asymmetric gonadal development in chickens, we compared the transcriptomes between left and right gonads of female chickens using bulk- and single cell (sc) -RNA sequencing (RNA-seq) approaches. Our bulk RNA-seq analysis of the female chicken gonads at E5 (HH26), E6.5 (HH30), E8 (HH34), and E9.5 (HH36) revealed significant differential gene expression between the left and right female chicken gonads, particularly in signaling pathways, cell cycle, and metabolic processes. Moreover, scRNA-seq analysis revealed that coelomic epithelial, interstitial, and pre-granulosa cells of the left gonads share a highly proliferative status, contributing to the asymmetric gonadal cell proliferation, which may be regulated by the TGFβ signaling pathway. Our findings demonstrate that dynamic cell-type-specific transcriptional profiles during embryogenesis play a vital role in the asymmetric gonadal development of female chickens.
2025-09-26 | GSE278919 | GEO
Project description:Asymmetric development, in which functional differences occur between left-right symmetrical organs, is widespread in organisms, including fish and mollusks. However, the asymmetry of symmetrical sensory structures in Haliotis discus hannai, a gastropod with a sensitive sensory system, remains unknown. This study analyzed the transcriptomes of three sensory structures (eyestalks, cephalic tentacles, and epipodial tentacles) to explore potential asymmetries in this species. RNA-seq revealed functional differences in sensory ability and sperm-egg recognition between right and left eyestalks, with cephalic tentacles displaying asymmetry in cytoskeletal organization and cell cycle regulation. Epipodial tentacles showed similar asymmetries, including immune response differences. Moreover, the cAMP-protein kinase A (PKA)-CREB-binding protein (CBP) signaling pathway responded asymmetrically, with PKA responding to activators and inhibitors on both sides and CBP showing a stronger response on the right. These findings provide insights into sensory asymmetry in mollusks and guidance for further investigations of the molecular mechanisms underlying asymmetry in symmetrical organs.
2025-01-07 | GSE285611 | GEO