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Control of CNS Synapse Development by γ-Protocadherin-Mediated Astrocyte–Neuron Contact
Journal article   Open access   Peer reviewed

Control of CNS Synapse Development by γ-Protocadherin-Mediated Astrocyte–Neuron Contact

Andrew M Garrett and Joshua A Weiner
The Journal of neuroscience, Vol.29(38), pp.11723-11731
09/23/2009
DOI: 10.1523/JNEUROSCI.2818-09.2009
PMCID: PMC2778296
PMID: 19776259
url
https://doi.org/10.1523/JNEUROSCI.2818-09.2009View
Published (Version of record) Open Access

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 γ-protocadherins (γ-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 -γ-null, we find that astrocyte–neuron γ-Pcdh contacts are critical for synaptogenesis in developing cultures. Synaptogenesis can eventually proceed among neurons cocultured with Pcdh -γ-null astrocytes, but only if these neurons themselves express the γ-Pcdhs. Consistent with this, restricted mutation of the Pcdh -γ 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.

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