Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Christopherson, Karen S; Ullian, Erik M; Stokes, Caleb C A; Mullowney, Christine E; Hell, Johannes W; Agah, Azin; Lawler, Jack; Mosher, Deane F; Bornstein, Paul; Barres, Ben A
Year of Publication: 2005
Journal: Cell
Volume: 120
Issue: 3
Pagination: 421-33
Date Published: 2005 Feb 11
Publication Language: eng
ISSN: 0092-8674
Keywords: Animals, Astrocytes, Biomarkers, Cell Communication, Cell Differentiation, Cells, Cultured, Central Nervous System, Culture Media, Conditioned, Down-Regulation, Mice, Mice, Knockout, Microscopy, Electron, Transmission, Nerve Growth Factors, Presynaptic Terminals, Rats, Rats, Sprague-Dawley, Synapses, Thrombospondin 1, Thrombospondins

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.

DOI: 10.1016/j.cell.2004.12.020
Alternate Journal: Cell