Directed differentiation of telencephalic precursors from embryonic stem cells

Nat Neurosci. 2005 Mar;8(3):288-96. doi: 10.1038/nn1402. Epub 2005 Feb 6.


We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells ( approximately 90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation ( approximately 35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or Islet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / physiology
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / physiology
  • Gene Expression Regulation, Developmental
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • Neurons / physiology
  • Nodal Protein* / antagonists & inhibitors
  • Nodal Protein* / metabolism
  • Telencephalon / cytology*
  • Telencephalon / embryology
  • Time Factors
  • Wnt3A Protein* / antagonists & inhibitors
  • Wnt3A Protein* / metabolism


  • Annexin A5
  • Culture Media, Serum-Free
  • Nerve Tissue Proteins
  • Nodal Protein
  • Wnt3A Protein