Tamoxifen induces cleft palate in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA591122 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10513879_1.fastq.gz | Fastqsanger.gz | |||
| SRR10513879_2.fastq.gz | Fastqsanger.gz | |||
| SRR10513880_1.fastq.gz | Fastqsanger.gz | |||
| SRR10513880_2.fastq.gz | Fastqsanger.gz | |||
| SRR10513881_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Tamoxifen (TAM), a widely-used drug in treating breast cancer, has been reported to be associated with craniofacial defects including micrognathia and cleft palate in humans. However, the exact effects of TAM on the developing palate remain unclear. In the present study, we conclude that excess TAM exposure causes cleft palate defect in mice by regulating MAPK pathways, which implicates the importance of tightly regulated MAPK signaling in palate development and provides a basis for further exploration of the molecular etiology of cleft palate defects caused by environmental factors.
2022-11-22 | GSE140836 | GEO
Project description:Cleft palate is a common congenital anomaly with a live birth prevalence estimated to be 1:2500 live births, that results from failure of growth, elevation, adhesion and/or fusion of the palatal shelves during embryogenesis. Mutations in the gene encoding the transcription factor p63 result in cleft palate in humans and mice. To study the roles of P63 in periderm migration and medial edge epithelia in mice sub-mucous cleft palate, ÎNp63alpha was ectopically expressed in the palatal epithelia using a transgenic approach.
2017-06-12 | E-MTAB-5289 | biostudies-arrayexpress
Project description:The overall goal of this project is to investigate the role of TGF-beta signaling in palate development in order to discover candidate therapeutics for preventing and treating congenital birth defects. Here, we conducted gene expression profiling of embryonic palatal tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate formation. To investigate the mechanism of cleft palate resulting from mutations in TGFBR2, we analyzed neural crest specific conditional inactivation of Tgfbr2 in mice (Tgfbr2fl/fl;Wnt1-Cre). We performed microarray analyses using the palatal tissue of Tgfbr2fl/fl;Wnt1-Cre mice at embryonic day E13.5 (prior to palatal fusion, n=6 per genotype) and E14.5 (during palatal fusion, n=5 per genotype) to examine the genes regulated by Tgf-beta during palate formation.
2011-11-29 | E-GEOD-22989 | biostudies-arrayexpress
Project description:The overall goal of this project is to investigate the role of TGF-beta signaling in palate development in order to discover candidate therapeutics for preventing and treating congenital birth defects. Here, we conducted gene expression profiling of embryonic palatal tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate formation.
2011-11-29 | GSE22989 | GEO
Project description:The Chinese sturgeon (Acipenser sinensis) is anadromous fish distributed in Yangtze River and East China Sea. In this study, we reported cleft-palate Chinese sturgeons in artificial population for the first time. In order to explore the genetic basis of palate malformation in A. sinensis, Illumina RNA-seq technology was used to analyze the transcriptome data of normal and cleft-palate individuals in farmed Chinese sturgeons. Raw reads were obtained and assembled into 808,612 unigenes, with an average length of 509.33 bp and an N50 of 574 bp. Sequence similarity analyses against four public databases (Nr, Uniprot, KEGG and COGs) found 158,642 unigenes that can be annotated. GABAergic synapse and TGF-β signal pathway were the most two enriched pathways with high Richfactor in the analyses of different expressed genes. In these two signal pathways, six genes (GABRA4, GS, GNS, S6K, PITX2, and BMP8) were found as cleft-palate genes in Chinese sturgeon. These findings contribute to our understanding of the genetic basis of cleft palate in sturgeon, while simultaneously adding to our knowledge about craniofacial development.
2018-03-24 | GSE112292 | GEO
Project description:In this study, we have investigated the molecular basis of Shh signalling during development of the secondary palate and how CNCC patterning and fate is influenced by the Shh signalling network. Using a gain-of-function mouse model to activate Smoothened (R26SmoM2) signalling in the palatal mesenchyme (Osr2-IresCre), we demonstrate ectopic Hh-Smo signalling results in fully penetrant cleft palate, disrupted oral-nasal patterning and defective palatine bone formation. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signalling in the secondary palate. Furthermore, we demonstrate that Wnt/BMP antagonists, in particular Sostdc1, are positively regulated by Hh signalling, concomitant with down-regulation of key regulators of osteogenesis and BMP signalling effectors. Microarray analysis was performed on excised palatal shelves from Osr2-IresCre+/- (wild-type) and Osr2-IresCre;Smo+/M2 (mutant) embryos at embryonic day (E)13.5. Osr2-IresCre (PMID:17941042) and R26SmoM2 (PMID:15107405) mice have been described previously.
2018-10-02 | E-MTAB-5518 | biostudies-arrayexpress
Project description:Background: In humans, cleft palate (CP) accounts for one of the largest number of birth defects with a complex genetic and environmental etiology. TGFM-NM-23 has been established as an important regulator of palatal fusion in mice and it has been shown that TGFM-NM-23-null mice exhibit CP without any other major deformities. However, the genes that regulate cellular decisions and molecular mechanisms maintained by the TGFM-NM-23 pathway throughout palatogenesis are predominantly unexplored. Our objective in this study was to analyze global transcriptome changes within the palate during different gestational ages within TGFM-NM-23 knockout mice to identify TGFM-NM-23-associated genes previously unknown to be associated with the development of cleft palate. We used deep sequencing technology, RNA-Seq, to analyze the transcriptome of TGFM-NM-23 knockout mice at crucial stages of palatogenesis, including palatal growth (E14.5), adhesion (E15.5), and fusion (E16.5). Results: The overall transcriptome analysis of TGFM-NM-23 wildtype mice (C57BL/6) reveals that almost 6000 genes were upregulated during the transition from E14.5 to E15.5 and more than 2000 were downregulated from E15.5 to E16.5. Using bioinformatics tools and databases, we identified the most comprehensive list of CP genes (n = 322) in which mutations cause CP either in humans or mice, and analyzed their expression patterns. The expression motifs of CP genes between TGFM-NM-23+/M-bM-^HM-^R and TGFM-NM-23M-bM-^HM-^R/M-bM-^HM-^R were not significantly different from each other, and the expression of the majority of CP genes remained unchanged from E14.5 to E16.5. Using these patterns, we identified 8 unique genes within TGFM-NM-23M-bM-^HM-^R/M-bM-^HM-^R mice (Chrng Foxc2, H19, Kcnj13, Lhx8, Meox2, Shh, and Six3), which may function as the primary contributors to the development of cleft palate in TGFM-NM-23M-bM-^HM-^R/M-bM-^HM-^R mice. When the significantly altered CP genes were overlaid with TGFM-NM-2 signaling, all of these genes followed the Smad-dependent pathway. Conclusions: Our study represents the first analysis of the palatal transcriptome of the mouse, as well as TGFM-NM-23 knockout mice, using deep sequencing methods. In this study, we characterized the critical regulation of palatal transcripts that may play key regulatory roles through crucial stages of palatal development. We identified potential causative CP genes in a TGFM-NM-23 knockout model, which may lead to a better understanding of the genetic mechanisms of palatogenesis and provide novel potential targets for gene therapy approaches to treat cleft palate. Palatal mRNA profiles of wild type (WT), TGFM-NM-23+/-, and TGFM-NM-23-/- mice at E14.5, E15.5, and E16.5 were generated by deep sequencing, in triplicate, using Illumina HiSeq2000
2013-03-29 | E-GEOD-45568 | biostudies-arrayexpress
Project description:Background: In humans, cleft palate (CP) accounts for one of the largest number of birth defects with a complex genetic and environmental etiology. TGFβ3 has been established as an important regulator of palatal fusion in mice and it has been shown that TGFβ3-null mice exhibit CP without any other major deformities. However, the genes that regulate cellular decisions and molecular mechanisms maintained by the TGFβ3 pathway throughout palatogenesis are predominantly unexplored. Our objective in this study was to analyze global transcriptome changes within the palate during different gestational ages within TGFβ3 knockout mice to identify TGFβ3-associated genes previously unknown to be associated with the development of cleft palate. We used deep sequencing technology, RNA-Seq, to analyze the transcriptome of TGFβ3 knockout mice at crucial stages of palatogenesis, including palatal growth (E14.5), adhesion (E15.5), and fusion (E16.5). Results: The overall transcriptome analysis of TGFβ3 wildtype mice (C57BL/6) reveals that almost 6000 genes were upregulated during the transition from E14.5 to E15.5 and more than 2000 were downregulated from E15.5 to E16.5. Using bioinformatics tools and databases, we identified the most comprehensive list of CP genes (n = 322) in which mutations cause CP either in humans or mice, and analyzed their expression patterns. The expression motifs of CP genes between TGFβ3+/− and TGFβ3−/− were not significantly different from each other, and the expression of the majority of CP genes remained unchanged from E14.5 to E16.5. Using these patterns, we identified 8 unique genes within TGFβ3−/− mice (Chrng Foxc2, H19, Kcnj13, Lhx8, Meox2, Shh, and Six3), which may function as the primary contributors to the development of cleft palate in TGFβ3−/− mice. When the significantly altered CP genes were overlaid with TGFβ signaling, all of these genes followed the Smad-dependent pathway. Conclusions: Our study represents the first analysis of the palatal transcriptome of the mouse, as well as TGFβ3 knockout mice, using deep sequencing methods. In this study, we characterized the critical regulation of palatal transcripts that may play key regulatory roles through crucial stages of palatal development. We identified potential causative CP genes in a TGFβ3 knockout model, which may lead to a better understanding of the genetic mechanisms of palatogenesis and provide novel potential targets for gene therapy approaches to treat cleft palate.
2013-03-29 | GSE45568 | GEO
Project description:Cleft palate is a common disorder of development resulting from failure of growth, migration, elevation, and osteogenic fusion of embryonic cranial neural crest-derived palatal shelves. Despite progress in recent decades, the molecular pathways involved in this failure are not well understood. Here, we present a multimodal, spatiotemporal transcriptomic profiling of the developing palate through integrated, unbiased single-cell and bulk RNA-sequencing and multiplexed in situ mRNA mapping of osteogenic cell lineages. We then show that loss of Pax9, a critical transcription factor orchestrator of Wnt signaling in palate development, results in increased expression of sclerostin (Sost), a known antagonist of Wnt signaling. Finally, we reveal that a single dose of sclerostin-neutralizing monoclonal antibody restores Wnt signaling and corrects cleft palate defects in utero in Pax9-/- mouse embryos.
2023-08-07 | GSE205448 | GEO
Project description:Cleft palate is a common disorder of development resulting from failure of growth, migration, elevation, and osteogenic fusion of embryonic cranial neural crest-derived palatal shelves. Despite progress in recent decades, the molecular pathways involved in this failure are not well understood. Here, we present a multimodal, spatiotemporal transcriptomic profiling of the developing palate through integrated, unbiased single-cell and bulk RNA-sequencing and multiplexed in situ mRNA mapping of osteogenic cell lineages. We then show that loss of Pax9, a critical transcription factor orchestrator of Wnt signaling in palate development, results in increased expression of sclerostin (Sost), a known antagonist of Wnt signaling. Finally, we reveal that a single dose of sclerostin-neutralizing monoclonal antibody restores Wnt signaling and corrects cleft palate defects in utero in Pax9-/- mouse embryos.
2023-08-07 | GSE205446 | GEO