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

Hum Mol Genet. 2019 Jan 1;28(1):64-73. doi: 10.1093/hmg/ddy329.


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.

Publication types

  • Research Support, Non-U.S. Gov't

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


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Repressor Proteins
  • Zebrafish Proteins
  • cohesins
  • HDAC8 protein, mouse
  • Histone Deacetylases