A neural crest origin for cohesinopathy heart defects

摘要: Mutations in subunits or regulators of cohesin cause a spectrum disorders humans known as the 'cohesinopathies'. Cohesinopathies, including best example Cornelia de Lange syndrome (CdLS), are characterized by broad spectrum, multifactorial developmental anomalies. Heart defects occur at high frequency and can reach up to 30% CdLS. The mechanisms which heart enigmatic, but assumed be origin. In this study, we depleted subunit Rad21 70-80% zebrafish cohesinopathy model. hearts Rad21-depleted animals were smaller, often failed loop, functioned less efficiently than size-matched controls. Functional deficiency was accompanied valve reduced ejection fraction. Interestingly, neural crest cells populate instead exhibited wandering behavior. Consequently, these also condense correctly into pharyngeal arches. Transcriptome analysis revealed that Wnt pathway, chemokine cadherin genes dysregulated time cardiac development. Our results give insight etiology cohesinopathies, raise possibility mild mutations may causative fraction congenital disease human populations.