An in vitro pathway from embryonic stem cells to neurons and glia

David I. Gottlieb, James E. Huettner

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Mouse embryonic stem (ES) cells can be induced to differentiate into neurons and glia in vitro. Induction protocols are straightforward and involve culture in the presence of retinoic acid. They result in an efficient conversion of undifferentiated ES cells to neural cells. Mature neurons produced have the key physiological, morphological and molecular properties of primary cultured neurons derived from the central nervous system. Most significantly, they form functional chemical synapses that utilize either glutamate, GABA or glycine as neurotransmitters. ES cell-derived glial cells also correspond well with their normal counterparts. During induction, ES cells undergo a series of developmental steps that resemble key stages in the early mouse embryo. This supports the hypothesis that the in vitro pathway is a valid model of the normal developmental pathway leading to neurons and glia. The in vitro system combines three experimental strengths. It is suitable for genetic manipulation, affords large numbers of cells and allows precise manipulation of the culture environment. It is thus suitable for a wide variety of mechanistic studies in the areas of neural development and cell biology.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalCells Tissues Organs
Issue number3-4
StatePublished - 1999


  • Embryonic stem cells
  • Glia
  • Neurons


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