PUBLICATION
Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation
- Authors
- Bottai, D., Spreafico, M., Pistocchi, A., Fazio, G., Adami, R., Grazioli, P., Canu, A., Bragato, C., Rigamonti, S., Parodi, C., Cazzaniga, G., Biondi, A., Cotelli, F., Selicorni, A., Massa, V.
- ID
- ZDB-PUB-180922-8
- Date
- 2018
- Source
- Human molecular genetics 28(1): 64-73 (Journal)
- Registered Authors
- Cotelli, Franco
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/physiology*
- Cell Differentiation/genetics
- Cell Differentiation/physiology
- Chromosomal Proteins, Non-Histone/genetics
- Chromosomal Proteins, Non-Histone/physiology*
- De Lange Syndrome/genetics*
- De Lange Syndrome/physiopathology
- Gene Expression Regulation/genetics
- Histone Deacetylases/genetics*
- Histone Deacetylases/metabolism
- Histone Deacetylases/physiology
- Male
- Mice
- Mice, Inbred C57BL
- Mutation/genetics
- Neural Stem Cells/physiology
- Neurons/physiology
- Phenotype
- Repressor Proteins/genetics
- Zebrafish
- Zebrafish Proteins
- PubMed
- 30239720 Full text @ Hum. Mol. Genet.
Citation
Bottai, D., Spreafico, M., Pistocchi, A., Fazio, G., Adami, R., Grazioli, P., Canu, A., Bragato, C., Rigamonti, S., Parodi, C., Cazzaniga, G., Biondi, A., Cotelli, F., Selicorni, A., Massa, V. (2018) Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation. Human molecular genetics. 28(1):64-73.
Abstract
Cornelia de Lange Syndrome (CdLS), which is reported to affect about 1 in 10,000 to 30,000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition.Cornelia de Lange syndrome can result from mutations in at least five genes: NIPBL (nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (RAD21 Cohesin Complex Component), and HDAC8 (Histone deacetylase 8). It is believed that mutations in these genes cause CdLS by impairing the function of the cohesin complex (to which all the aforementioned genes contribute to the structure or function), disrupting gene regulation during critical stages of early development.Since intellectual disorder might result from alterations in neural development, in this work, we studied the role of Hdac8 gene in mouse neural stem cells and in vertebrate (D.rerio) brain development by knock-down and chemical inhibition experiments. An underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs and in zebrafish embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping