Dyrk1A influences neuronal morphogenesis through regulation of cytoskeletal dynamics in mammalian cortical neurons

Cereb Cortex. 2012 Dec;22(12):2867-77. doi: 10.1093/cercor/bhr362. Epub 2012 Jan 2.


Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cytoskeleton / metabolism*
  • Cytoskeleton / pathology
  • Down Syndrome / metabolism*
  • Down Syndrome / pathology
  • Dyrk Kinases
  • Mice
  • Mice, Transgenic
  • Neurogenesis*
  • Neurons / metabolism*
  • Neurons / pathology*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*


  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases