Gene expression profiling of Tgfbr2 mutant mouse models of cleft palate
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22989 | GEO | 2011/11/29
SECONDARY ACCESSION(S): PRJNA127771
REPOSITORIES: GEO
Similar Datasets
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 regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells 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, which is among the most common congenital birth defects and observed in many syndromic conditions. To investigate the adverse effects of dysfunctional TGF-Beta signaling on the cellular metabolism of palatal mesenchyme during palatogenesis, we analyzed mice with a neural crest cell-specific conditional inactivation of Tgfbr2 (Tgfbr2fl/fl;Wnt1-Cre). We performed microarray analyses of primary mouse embryonic palatal mesenchymal cells of Tgfbr2fl/fl;Wnt1-Cre mutant mice and Tgfbr2fl/fl control mice, collected at embryonic day 13.5 (n=4 per genotype) and cultured with standard media (DMEM with supplements). Cells were collected after 2 passages.
2013-10-01 | E-GEOD-46150 | biostudies-arrayexpress
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 regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells 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, which is among the most common congenital birth defects and observed in many syndromic conditions.
2013-10-01 | GSE46150 | GEO
Project description:The overall goal of this project is to investigate the role of TGF-beta signaling in epithelial cells as it pertains to the orientation of muscle fibers in the soft palate during embryogenesis. Here, we first conducted gene expression profiling of the anterior and posterior portions of the palate from wild-type mice. In addition, we also conducted gene expression profiling of the posterior palate in mutant mice with an epithelium-specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of submucosal cleft palate, which is a congenital birth defect commonly observed in many syndromic conditions. To investigate the adverse effects of dysfunctional TGF-Beta signaling on tissue-tissue interaction between the palatal epithelium and myofibers during palatogenesis, we analyzed mice with an epithelial cell-specific conditional inactivation of Tgfbr2 (Tgfbr2fl/fl;K14-Cre). We performed microarray analyses of anterior palatal tissue and posterior palatal tissue of E15.5 Tgfbr2fl/fl control mice (n=5, each region), and posterior palatal tissue of Tgfbr2fl/fl;K14-Cre mutant mice, collected at embryonic day 15.5 (n=5). Control samples and mutant samples are from separate litters.
2013-10-01 | E-GEOD-46211 | biostudies-arrayexpress
Project description:The overall goal of this project is to investigate the role of Erk2-mediated signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of palate tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Erk2 gene. The latter mice exhibit micrognathia, tongue defects and cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions. To investigate the adverse effects of dysfunctional ERK signaling on the cellular metabolism of palatal mesenchyme during palatogenesis, we analyzed mice with a neural crest cell-specific conditional inactivation of Erk2 (Erk2fl/fl;Wnt1-Cre). We performed microarray analyses of primary mouse embryonic palatal mesenchymal cells of Erk2fl/fl;Wnt1-Cre mutant mice and Erk2fl/fl control mice, collected at embryonic day 13.5 (n=3 per genotype) and E14.5 (n=5 per genotype).
2015-12-11 | E-GEOD-67087 | biostudies-arrayexpress
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
Project description:The overall goal of this project is to investigate the role of Erk2-mediated signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of palate tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Erk2 gene. The latter mice exhibit micrognathia, tongue defects and cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.
2015-12-11 | GSE67087 | 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