Modeling Cornelia de Lange syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation
| Autor: | Gianni Cazzaniga, Paolo Grazioli, Chiara Parodi, Cinzia Bragato, Silvia Rigamonti, Valentina Massa, Adriana Canu, Daniele Bottai, Anna Pistocchi, Andrea Biondi, Raffaella Adami, Marco Spreafico, Franco Cotelli, Grazia Fazio, Angelo Selicorni |
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| Přispěvatelé: | 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cornelia de Lange Syndrome Cohesin complex MED/03 - GENETICA MEDICA Chromosomal Proteins Non-Histone HDAC8 Gene Cell Cycle Proteins Biology medicine.disease_cause Histone Deacetylases Mice 03 medical and health sciences Neural Stem Cells Genetic De Lange Syndrome Genetics medicine Animals Zebrafish Molecular Biology Genetics (clinical) Neurons Regulation of gene expression 0303 health sciences Mutation Gene knockdown 030305 genetics & heredity Cell Differentiation General Medicine Zebrafish Proteins medicine.disease biology.organism_classification Cell biology Mice Inbred C57BL Repressor Proteins Phenotype Gene Expression Regulation Neural development |
| Popis: | Cornelia de Lange syndrome (CdLS), which is reported to affect ∼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. CdLS can result from mutations in at least five genes: nipped-B-like protein, structural maintenance of chromosomes 1A, structural maintenance of chromosomes 3, RAD21 cohesin complex component and histone deacetylase 8 (HDAC8). 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 (NSCs) and in vertebrate (Danio rerio) brain development by knockdown and chemical inhibition experiments. Underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs or in zebrafish embryos. |
| Databáze: | OpenAIRE |
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