| Title | Control of CNS synapse development by {gamma}-protocadherin-mediated astrocyte-neuron contact. | | Author(s) | Garrett AM, Weiner JA | | Institution | Department of Biology, The University of Iowa, Iowa City, 52242, USA. | | Source | J Neurosci 2009 Sep 23; 29(38):11723-31. | | MeSH | Animals
Animals, Newborn
Astrocytes
Cadherins
Coculture Techniques
Culture Media, Conditioned
Fluorescent Antibody Technique
Hippocampus
In Situ Hybridization, Fluorescence
Mice
Mice, Knockout
Mice, Transgenic
Microscopy, Confocal
Mutation
Neurons
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord
Synapses
| | Abstract | Recent studies indicate that astrocytes, whose processes enwrap synaptic terminals, promote synapse formation both by releasing soluble factors and through contact-dependent mechanisms. Although astrocyte-secreted synaptogenic factors have been identified, the molecules underlying perisynaptic astroctye-neuron contacts are unknown. Here we show that the gamma-protocadherins (gamma-Pcdhs), a family of 22 neuronal adhesion molecules encoded by a single gene cluster, are also expressed by astrocytes and localize to their perisynaptic processes. Using cocultures in which either astrocytes or neurons are Pcdh-gamma-null, we find that astrocyte-neuron gamma-Pcdh contacts are critical for synaptogenesis in developing cultures. Synaptogenesis can eventually proceed among neurons cocultured with Pcdh-gamma-null astrocytes, but only if these neurons themselves express the gamma-Pcdhs. Consistent with this, restricted mutation of the Pcdh-gamma cluster in astrocytes in vivo significantly delays both excitatory and inhibitory synapse formation. Together, these results identify the first known contact-dependent mechanism by which perisynaptic astrocyte processes promote synaptogenesis. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19776259 |
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