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Notch3 is an asymmetric gene and a modifier of heart looping defects in Nodal mouse mutants

ABSTRACT: Notch3 is an asymmetric gene and a modifier of heart looping defects in Nodal mouse mutants

PROVIDER: PRJNA994014 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25244808_1.fastq.gz	Fastqsanger.gz
	SRR25244808_2.fastq.gz	Fastqsanger.gz
	SRR25244809_1.fastq.gz	Fastqsanger.gz
	SRR25244809_2.fastq.gz	Fastqsanger.gz
	SRR25244810_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Notch3 is an asymmetric gene and a modifier of heart looping defects in Nodal mouse mutants

Project description:The TGFb secreted factor NODAL is a major left determinant required for the asymmetric morphogenesis of visceral organs, including the heart. Yet, when this signalling is absent, shape asymmetry, for example of the embryonic heart loop, is not fully abrogated, indicating that there are other factors regulating left-right patterning. Here, we used a tailored transcriptomic approach to screen for genes asymmetrically expressed in the field of heart progenitors. We thus identify Notch3 as a novel left-enriched gene and validate, by quantitative in situ hybridization, its transient asymmetry in the lateral plate mesoderm and node crown, overlapping with Nodal. In mutant embryos, we analysed the regulatory hierarchy and demonstrate that Nodal in the lateral plate mesoderm amplifies Notch3 asymmetric expression. The function of Notch3 was uncovered in an allelic series of mutants. In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve, in addition to its known role in coronary arteries. In compound mutants, we reveal that Notch3 acts as a genetic modifier of heart looping direction and shape defects in Nodal mutants. Whereas Notch3 was previously mainly associated with the CADASIL syndrome, our observations in the mouse and a human cohort support a novel role in congenital heart defects and laterality defects.

2025-01-31 | GSE237126 | GEO

Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop

Project description:The secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis.

2020-11-09 | GSE148123 | GEO

NOTCH3-IC

Project description:NOTCH3-IC

| PRJNA480489 | ENA

Nodal

Project description:Mus musculus Nodal, nodal [Source:MGI Symbol;Acc:MGI:97359], is differentially expressed in 30 experiment(s);

| ENSMUSG00000037171 | ExpressionAtlas

Nodal

Project description:Mus musculus Nodal, nodal [Source:MGI Symbol;Acc:MGI:97359], is expressed in 19 baseline experiment(s);

| ENSMUSG00000037171 | ExpressionAtlas

NODAL

Project description:Monodelphis domestica NODAL, nodal growth differentiation factor [Source:NCBI gene;Acc:100023464], is expressed in 2 baseline experiment(s);

| ENSMODG00000012158 | ExpressionAtlas

Nodal

Project description:Rattus norvegicus Nodal, nodal growth differentiation factor [Source:RGD Symbol;Acc:1305994], is expressed in 1 baseline experiment(s);

| ENSRNOG00000000556 | ExpressionAtlas

NODAL

Project description:Oryctolagus cuniculus NODAL, nodal growth differentiation factor [Source:HGNC Symbol;Acc:HGNC:7865], is expressed in 1 baseline experiment(s);

| ENSOCUG00000008685 | ExpressionAtlas

NODAL

Project description:Homo sapiens NODAL, nodal growth differentiation factor [Source:HGNC Symbol;Acc:HGNC:7865], is expressed in 31 baseline experiment(s);

| ENSG00000156574 | ExpressionAtlas

NODAL

Project description:Macaca mulatta NODAL, nodal growth differentiation factor [Source:HGNC Symbol;Acc:HGNC:7865], is expressed in 1 baseline experiment(s);

| ENSMMUG00000023171 | ExpressionAtlas

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