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Heart fields auto-regulate second heart field cell fate via Wnt secretion

ABSTRACT: The purpose of this study was to identify the source of Wnt signals that lead to development/proliferation of the heart fields, particularly the second heart field. To this end, we knocked out Wntless (Wls), which is necessary for Wnt secretion, in Mesp1+ lineage cells. We performed single cell RNA-seq to better identify the source of Wnt signals and the effects of the loss of Wnt secretion in mesoderm.

ORGANISM(S): Mus musculus

PROVIDER: GSE165300 | GEO | 2021/01/23

REPOSITORIES: GEO

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Heart fields auto-regulate second heart field cell fate via Wnt secretion

Project description:Heart fields auto-regulate second heart field cell fate via Wnt secretion

| PRJNA694043 | ENA

Expression analysis of genes regulated by RBPJ (Notch) and Axin2 (Wnt) mediated signaling in mouse cardiogenesis at E9.25

Project description:Progenitor cells of the first and second heart fields (FHF and SHF) depend on cardiac-specific transcription factors for their differentiation. In mouse mutant embryos, we define the hierarchy of signaling events that controls the expression of cardiac-specific transcription factors during commitment of SHF progenitors at E9.25. Wnt and Bmp act downstream of Notch/RBPJ at this developmental stage. Mutation of Axin2, the negative regulator of canonical Wnt signaling, enhances Wnt and Bmp signals and suffices to rescue the cardiac differentiation arrest caused by loss of RBPJ. By analysis of isolated cardiac progenitors, embryo cultures in the presence of pharmacological inhibitors, and Bmp triple mutants, we could classify the expression of heart-specific transcription factors of SHF progenitors according to their dependence on either Wnt or Bmp signals, Nkx2-5, Isl1, Baf60c and Gata4, SRF, Mef2c, respectively. Total RNA from whole embryonic hearts of control mice was compared to MesP1-cre:RBPJlox/lox (KO), MesP1-cre:RBPJlox/lox//Axin2-/- (DKO), MesP1-cre:RBPJlox/+//Axin2-/- (hetDKO) and MesP1-cre:RBPJlox/lox//Axin2+/- (DKOhet) mutant mouse embryos.

2012-06-20 | E-GEOD-36804 | biostudies-arrayexpress

SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion

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2018-10-16 | PXD010632 | Pride

Wnt ligands from the embryonic surface ectoderm regulate bimetallic strip optic cup morphogenesis in the mouse

Project description:Wnt signaling in early eye development, specifically the lens placode shows expression of 12 out of 19 Wnt ligands. We these Wnt activities were suppressed using conditional deletion of Wntless, dramatic phenotypic changes in morphogensis occurred. Microarray analysis of the genes that were changed in response to deletion of Wnt ligands in the developing eye region show direct or indirect responses from the surface ectoderm to the developing RPE and optic cup curvature, creating an overal shape change phenotype in the bilayerd epithelium of the optic cup. Mouse embryos at embryonic stage e10.5 were disected into pbs and eye regions were disected and removed for RNA extraction and hybridization to Affymetrix microarrays. We sought to identify the genes that were changed in response to deletion of Wls from the developing surface ectoderm of the eye region. Genes changed could be the direct or indirect result from deleltion of Wls from the surface ectoderm using the LeCre recombinase gene as a tool for analysis.

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RNAseq transcriptomic signature associated depletion of Evi/Wls in epidermal sheets of mice, expression analysis of epidermal sheets of Evi/Wls knockout and wildtype mice

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2013-07-24 | E-MTAB-1613 | biostudies-arrayexpress

Identification of endothelial genes co-regulated upon endothelial Evi/Wls and Rspo3 deletion

Project description:Inducible endothelial Rspo3 deletion resulted in perturbed developmental and tumor vascular remodeling. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified novel target genes, which could be linked to WNT/Ca2+/NFAT signaling. In summary, the study identifies endothelial RSPO3-driven non canonical WNT/Ca2+/NFAT signaling as critical maintenance pathway of the remodeling vasculature.

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Precardiac Organoids Form Two Heart Fields via Bmp/Wnt Signaling

Project description:The discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease.

2018-06-23 | GSE116128 | GEO

Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus

Project description:We studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to eliminating Wntless (Wls) in a subset of cortical progenitors with Gfap-Cre.

2020-10-01 | GSE157983 | GEO

Early lineage restriction and regional segregation during mammalian heart development

Project description:Cardiac development arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during the early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Altogether, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occurs very early during gastrulation. We used microarrays to characterize the molecular mechanisms that control Mesp1 progenitor specification and lineage segregation during the early stage of cardiac mesoderm formation, 50 Mesp1 H2B-GFP+ or Mesp1 H2B-GFP- cells at E6.5 or E7.5 from mouse embryos were sorted for RNA extraction, amplification and hybridization on Affimetrix microarrays. Microaarrays were performed on Mouse Genome 430 PM strip Affymetrix array. The overall design was repeated in two different biological samples.

2014-07-10 | E-GEOD-59033 | biostudies-arrayexpress

Profiling of chromatin accessibility by ATAC-seq in hematopoietic LSK cells and leukemic stem cells of AML

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