Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis

Karen S. Christopherson, Erik M. Ullian, Caleb C A Stokes, Christine E. Mullowney, Johannes W Hell, Azin Agah, Jack Lawler, Deane F. Mosher, Paul Bornstein, Ben A. Barres

Research output: Contribution to journalArticle

955 Scopus citations

Abstract

The establishment of neural circuitry requires vast numbers of synapses to be generated during a specific window of brain development, but it is not known why the developing mammalian brain has a much greater capacity to generate new synapses than the adult brain. Here we report that immature but not mature astrocytes express thrombospondins (TSPs)-1 and -2 and that these TSPs promote CNS synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work in concert with other, as yet unidentified, astrocyte-derived signals to produce functional synapses. These studies identify TSPs as CNS synaptogenic proteins, provide evidence that astrocytes are important contributors to synaptogenesis within the developing CNS, and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development.

Original languageEnglish (US)
Pages (from-to)421-433
Number of pages13
JournalCell
Volume120
Issue number3
DOIs
StatePublished - Feb 11 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Christopherson, K. S., Ullian, E. M., Stokes, C. C. A., Mullowney, C. E., Hell, J. W., Agah, A., Lawler, J., Mosher, D. F., Bornstein, P., & Barres, B. A. (2005). Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell, 120(3), 421-433. https://doi.org/10.1016/j.cell.2004.12.020