文献库 文献相关信息
- 题目:
- Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts.
- 作者:
- Pistocchi(A),Fazio(G),Cereda(A),Ferrari(L),Bettini(L R),Messina(G),Cotelli(F),Biondi(A),Selicorni(A),Massa(V)
- 状态:
- 发布时间2013-10-18 , 更新时间 2015-04-22
- 期刊:
- Cell Death Dis
- 摘要:
- Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the 'cohesin complex'. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.
- 语言:
- eng
- DOI:
DataTable pData
微信公众号
关注微信订阅号，实时查看信息，关注医学生物学动态。
版权所有 © 2025.Genelibs 济南弘晖生物技术有限公司 鲁ICP备13024435号-2
