The Journal of Neuroscience, September 23, 2009, 29(38):11723-11731; doi:10.1523/JNEUROSCI.2818-09.2009
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Development/Plasticity/Repair
Control of CNS Synapse Development by
-Protocadherin-Mediated Astrocyte–Neuron Contact
Andrew M. Garrett and
Joshua A. Weiner
Department of Biology, Neuroscience Graduate Program, The University of Iowa, Iowa City, Iowa 52242
Correspondence should be addressed to Joshua A. Weiner, Department of Biology, Neuroscience Graduate Program, The University of Iowa, 143 Biology Building, Iowa City, IA 52242. Email: joshua-weiner{at}uiowa.edu
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
-protocadherins (
-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-
-null, we find that astrocyte–neuron
-Pcdh contacts are critical for synaptogenesis in developing cultures. Synaptogenesis can eventually proceed among neurons cocultured with Pcdh-
-null astrocytes, but only if these neurons themselves express the
-Pcdhs. Consistent with this, restricted mutation of the Pcdh-
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.
Received June 15, 2009;
revised July 17, 2009;
accepted Aug. 1, 2009.
Correspondence should be addressed to Joshua A. Weiner, Department of Biology, Neuroscience Graduate Program, The University of Iowa, 143 Biology Building, Iowa City, IA 52242. Email: joshua-weiner{at}uiowa.edu
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