Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy

Cell Stem Cell. 2011 Apr 8;8(4):434-44. doi: 10.1016/j.stem.2011.02.004. Epub 2011 Mar 31.


Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting a variety of organs, including the central nervous system. By using neuronal progeny derived from human embryonic stem cells carrying the causal DM1 mutation, we have identified an early developmental defect in genes involved in neurite formation and the establishment of neuromuscular connections. Differential gene expression profiling and quantitative RT-PCR revealed decreased expression of two members of the SLITRK family in DM1 neural cells and in DM1 brain biopsies. In addition, DM1 motoneuron/muscle cell cocultures showed alterations that are consistent with the known role of SLITRK genes in neurite outgrowth, neuritogenesis, and synaptogenesis. Rescue and knockdown experiments suggested that the functional defects can be directly attributed to SLITRK misexpression. These neuropathological mechanisms may be clinically significant for the functional changes in neuromuscular connections associated with DM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Embryonic Stem Cells / pathology*
  • Embryonic Stem Cells / ultrastructure
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Humans
  • Membrane Proteins / genetics*
  • Mutation*
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / pathology
  • Nerve Tissue Proteins / genetics*
  • Neurites / pathology*
  • Synapses / pathology*


  • Membrane Proteins
  • Nerve Tissue Proteins
  • SLITRK1 protein, human

Associated data

  • GEO/GSE7214