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Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC.

Astrocytes regulate synaptic connectivity in the CNS through secreted signals. Here we identified two astrocyte-secreted proteins, hevin and SPARC, as regulators of excitatory synaptogenesis in vitro and in vivo. Hevin induces the formation of synapses between cultured rat retinal ganglion cells. SPARC is not synaptogenic, but specifically antagonizes synaptogenic function of hevin. Hevin and SPARC are expressed by astrocytes in the superior colliculus, the synaptic target of retinal ganglion cells, concurrent with the excitatory synaptogenesis. Hevin-null mice had fewer excitatory synapses; conversely, SPARC-null mice had increased synaptic connections in the superior colliculus. Furthermore, we found that hevin is required for the structural maturation of the retinocollicular synapses. These results identify hevin as a positive and SPARC as a negative regulator of synapse formation and signify that, through regulation of relative levels of hevin and SPARC, astrocytes might control the formation, maturation, and plasticity of synapses in vivo.

Pubmed ID: 21788491


  • Kucukdereli H
  • Allen NJ
  • Lee AT
  • Feng A
  • Ozlu MI
  • Conatser LM
  • Chakraborty C
  • Workman G
  • Weaver M
  • Sage EH
  • Barres BA
  • Eroglu C


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 9, 2011

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA15043
  • Agency: NIGMS NIH HHS, Id: GM40711

Mesh Terms

  • Animals
  • Astrocytes
  • Calcium-Binding Proteins
  • Central Nervous System
  • Culture Media, Conditioned
  • Extracellular Matrix Proteins
  • HEK293 Cells
  • Humans
  • Mice
  • Neurogenesis
  • Osteonectin
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells
  • Superior Colliculi
  • Synapses