Distinct Stages of Myelination Regulated by γ-Secretase and Astrocytes in a Rapidly Myelinating CNS Coculture System

Trent A. Watkins, Ben Emery, Sara Mulinyawe, Ben A. Barres

Research output: Contribution to journalArticle

225 Scopus citations


Mechanistic studies of CNS myelination have been hindered by the lack of a rapidly myelinating culture system. Here, we describe a versatile CNS coculture method that allows time-lapse microscopy and molecular analysis of distinct stages of myelination. Employing a culture architecture of reaggregated neurons fosters extension of dense beds of axons from purified retinal ganglion cells. Seeding of oligodendrocyte precursor cells on these axons results in differentiation and ensheathment in as few as 3 days, with generation of compact myelin within 6 days. This technique enabled (1) the demonstration that oligodendrocytes initiate new myelin segments only during a brief window early in their differentiation, (2) identification of a contribution of astrocytes to the rate of myelin wrapping, and (3) molecular dissection of the role of oligodendrocyte γ-secretase activity in controlling the ensheathment of axons. These insights illustrate the value of this defined system for investigating multiple aspects of CNS myelination.

Original languageEnglish (US)
Pages (from-to)555-569
Number of pages15
Issue number4
StatePublished - Nov 26 2008




ASJC Scopus subject areas

  • Neuroscience(all)

Cite this