Similar Datasets
Project description:FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (FlncgKO) and cardiomyocyte-specific knockout (FlnccKO) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of β1 integrin specifically in the myocardium of FlncgKO mice. Although deleting β1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both β1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with β1 integrin to maintain the structural integrity of myocardium during mammalian heart development.
| S-EPMC9907827 | biostudies-literature
Project description:Filamin C is Essential for Mammalian Myocardial Integrity
| PRJNA922494 | ENA
Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of these complexes, physiological roles for this domain remain undefined. We screened an N-ethyl-N-nitrosurea (ENU) mutagenized library for ARID domain point mutations and generated an Arid1a/Baf250a hypomorphic allele. The mutant ARID1a (V1068G) protein is stably expressed at wild-type levels, and it is capable of assembling into a SWI/SNF complex with in vitro mononucleosome disruption activity. However, its capacity to bind DNA is lost. Consistent with defective DNA binding, mutant protein occupancy at known SWI/SNF target genes is decreased. Loss of DNA binding is associated with concurrent changes in SWI/SNF target gene expression. Mutant embryos manifest heart defects, fail to establish proper yolk sac vasculature, and exhibit hemorrhaging. As a result of these phenotypes, mutant embryos fail to establish proper circulation, culminating in ischemic arrest in utero between days 9.5 and 11.5. These data support a role for ARID1a-containing, BAF-A complexes in heart and extraembryonic vascular development, and indicate the ARID domain of ARID1a is essential in this regard. Hence, intrinsic ARID subunit-DNA interactions are required for normal SWI/SNF function in vivo. Four-condition experiment, wild-type vs Baf250a/Arid1a^V1068G/V1068G yolk sacs isolated at E8.5 and E9.5. Biological replicates: 3 per condition.
2012-01-15 | E-GEOD-32116 | biostudies-arrayexpress
Project description:In order to understand genes expressed during posterior second heart field (pSHF) development, we performed microdissections of the region for transcriptomic analysis at mouse embryonic day 9.5.
2015-11-17 | GSE75077 | GEO
Project description:Time course of early development of peripheral nerve, from embryonic day 9.5 to postnatal day 0. Origin of samples: mouse embryos expressing green fluorescent protein (GFP) in neural crest stem cells and later glial cells under the control of the proteolipid protein gene (Plp) promoter. At E9.5 the trunk region was dissected out. At E12, E14, E16, E18 and P0 the sciatic nerve was taken. GFP-expressing cells were isolated by FACS sorting. Three or 4 separate batches of embryos analyzed at each stage. Keywords: time-course
2004-02-21 | GSE972 | GEO
Project description:We have developed gene-targeted mice with deletion of Nkx2.5. Embryos were isolated at embryonic day 9.5 and the middle third containing the heart was run on Affymetrix Mu11kA and Mu11kB arrays. For more information about this model see http://cardiogenomics.med.harvard.edu/groups/proj1/pages/csx_home.html Keywords = Congenital heart disease Keywords: other
2002-08-02 | GSE78 | GEO
Project description:Embryonic gene expression intricately reflects anatomical context, developmental stage, and cell type. To address whether the precise spatial origins of cardiac cells can be deduced solely from their transcriptional profiles, we established a genome-wide expression database from 118, 949, and 1166 single murine heart cells at embryonic days (e)8.5, 9.5, and 10.5, respectively. We segregated these cells by type using unsupervised bioinformatic analysis and identified novel chamber-specific genes. Using a random forest algorithm, we reconstructed the spatial origin of single e9.5 and e10.5 cardiomyocytes with 92.0+/-3.2% and 91.2+/-2.8% accuracy respectively (99.4+/-1.0% and 99.1+/-1.1% if a +/-1 zone margin is permitted) and predicted the second heart field distribution of Isl1-lineage descendants. When applied to Nkx2-5-/- cardiomyocytes from murine e9.5 hearts, we showed their transcriptional alteration and lack of ventricular phenotype. Our database and zone classification algorithm will enable the discovery of novel mechanisms in early cardiac development and disease.
2016-11-10 | GSE89465 | GEO
Project description:Embryonic gene expression intricately reflects anatomical context, developmental stage, and cell type. To address whether the precise spatial origins of cardiac cells can be deduced solely from their transcriptional profiles, we established a genome-wide expression database from 118, 949, and 1166 single murine heart cells at embryonic days (e)8.5, 9.5, and 10.5, respectively. We segregated these cells by type using unsupervised bioinformatic analysis and identified novel chamber-specific genes. Using a random forest algorithm, we reconstructed the spatial origin of single e9.5 and e10.5 cardiomyocytes with 92.0+/-3.2% and 91.2+/-2.8% accuracy respectively (99.4+/-1.0% and 99.1+/-1.1% if a +/-1 zone margin is permitted) and predicted the second heart field distribution of Isl1-lineage descendants. When applied to Nkx2-5-/- cardiomyocytes from murine e9.5 hearts, we showed their transcriptional alteration and lack of ventricular phenotype. Our database and zone classification algorithm will enable the discovery of novel mechanisms in early cardiac development and disease.
2016-11-10 | GSE76118 | GEO
Project description:FLNc, the muscle-specific isoform of the filamin family, is a multi-adaptor protein, comprising 1 amino-terminal actin-binding (ABD) domain followed by 24 immunoglobulin-like (Ig) domains. While FLNc can form homodimers via the last Ig-like domain and thus function as an actin-crosslinker like the other filamins, it features a unique insertion of 82 amino acids (aa) in domain 20. This insert was not only shown to mediate the interaction to several FLNc binding partners, but also to contain an Akt-mediated phosphorylation site at S2234 of mouse FLNc (mFLNc). To reveal novel proteins in the nano-environment of FLNc within myotubes under mild electrical pulse stimulation conditions, we applied a quantitative BioID appraoch.
2021-07-12 | PXD009159 | Pride
Project description:Histone deacetylase 3 deletion in the embryonic heart at day E9.5
| PRJNA270256 | ENA