Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

Nat Commun. 2017 Mar 10;8:14666. doi: 10.1038/ncomms14666.

Abstract

The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Dentate Gyrus / cytology
  • Dentate Gyrus / growth & development
  • Dentate Gyrus / metabolism*
  • Gene Expression Regulation, Developmental
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics*
  • Neurons / cytology
  • Neurons / metabolism*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Semaphorins / genetics*
  • Semaphorins / metabolism
  • Signal Transduction
  • Stereotaxic Techniques
  • Temporal Lobe / cytology
  • Temporal Lobe / growth & development
  • Temporal Lobe / metabolism

Substances

  • Antigens, CD
  • Integrin beta1
  • Nerve Tissue Proteins
  • Plxna3 protein, mouse
  • Receptors, Cell Surface
  • Sema7a protein, mouse
  • Semaphorins