Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells

Yuntao Duan, Shih Hsiu Wang, Juan Song, Yevgeniya Mironova, Guo li Ming, Alex L. Kolodkin, Roman J. Giger

Research output: Contribution to journalArticlepeer-review

Abstract

Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A-/- GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A-/- mutants, PlexinA2-/- mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A-/- mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders.

Original languageEnglish (US)
Article numbere04390
JournaleLife
Volume3
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • 3D electron microscopy
  • dentate granule cells
  • hippocampus
  • mouse
  • neuroscience
  • plexin
  • semaphorin
  • synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells'. Together they form a unique fingerprint.

Cite this