Mutations in subunits or regulators of cohesin cause a spectrum of disorders in humans known as the 'cohesinopathies'. Cohesinopathies, including the best known example Cornelia de Lange Syndrome (CdLS), are characterised by broad spectrum, multifactorial developmental anomalies. Heart defects occur at high frequency and can reach up to 30% in CdLS. The mechanisms by which heart defects occur are enigmatic, but assumed to be developmental in origin. In this study, we depleted cohesin subunit Rad21 by 70-80% in a zebrafish cohesinopathy model. The hearts of Rad21-depleted animals were smaller, often failed to loop, and functioned less efficiently than size-matched controls. Functional deficiency was accompanied by valve defects and reduced ejection fraction. Interestingly, neural crest cells failed to populate the heart and instead exhibited a wandering behavior. Consequently, these cells also failed to condense correctly into pharyngeal arches. Transcriptome analysis revealed that Wnt pathway, chemokine and cadherin genes are dysregulated at the time of cardiac neural crest development. Our results give insight into the etiology of heart defects in the cohesinopathies, and raise the possibility that mild mutations in cohesin genes may be causative of a fraction of congenital heart disease in human populations.
This research output has an Altmetric Attention Score of 69. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 December 2015.
All research outputs
#648,985
of 26,184,649 outputs
Outputs from Human Molecular Genetics
#75
of 8,362 outputs
Outputs of similar age
#8,915
of 287,414 outputs
Outputs of similar age from Human Molecular Genetics
#4
of 123 outputs
Altmetric has tracked 26,184,649 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,362 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.4. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 287,414 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 123 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.
