CyclinD1 Down-Regulation and Increased Apoptosis Are Common Features of Cohesinopathies.

摘要: Abstract Genetic variants within components of the cohesin complex (NIPBL, SMC1A, SMC3, RAD21, PDS5, ESCO2, HDAC8) are believed to be responsible for a spectrum human syndromes known as "cohesinopathies" that includes Cornelia de Lange Syndrome (CdLS). CdLS is multiple malformation syndrome affecting almost any organ and causing severe developmental delay. Cohesinopathies seem caused by dysregulation specific pathways downstream mutations in components. However, it still unclear how different affect output gene regulation. In this study, zebrafish embryos SMC1A-mutated patient-derived fibroblasts were used analyze abnormalities induced SMC1A loss function. We show knockdown smc1a impairs neural development, increases apoptosis, specifically down-regulates Ccnd1 levels. The same down-regulation targets observed patient fibroblasts. Previously, we have demonstrated haploinsufficiency NIPBL produces similar effects patients indicating possible common feature neurological defects mental retardation cohesinopathies. Interestingly, expression analysis Smc1a Nipbl developing mouse reveals pattern hindbrain, suggesting role cohesins development vertebrates. J. Cell. Physiol. 231: 613-622, 2016. © 2015 Wiley Periodicals, Inc.