Modeling Cornelia de Lange syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation

Daniele Bottai, Marco Spreafico, Anna Pistocchi, Grazia Fazio, Raffaella Adami, Paolo Grazioli, Adriana Canu, Cinzia Bragato, Silvia Rigamonti, Chiara Parodi, Gianni Cazzaniga, Andrea Biondi, Franco Cotelli, Angelo Selicorni, Valentina Massa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)64-73
Number of pages10
JournalHuman Molecular Genetics
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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