Impaired hippocampal neurogenesis and vascular formation in ephrin-A5-deficient mice

Stem Cells. 2010 May;28(5):974-83. doi: 10.1002/stem.427.


Neurogenesis occurs throughout the life in the mammalian brain. The hippocampal dentate gyrus (DG) is one of the major regions of the adult neurogenesis, where neural stem/progenitor cells continuously generate new granule neurons, although molecular mechanisms underlying generation and maintenance of newly born neurons are still elusive. Here we show that ephrin-A5, a ligand for Eph receptor tyrosine kinases, plays multiple roles in both neurogenesis and vascular formation in the adult hippocampus. In mice lacking ephrin-A5 function, cell proliferation and survival of newborn neurons were severely reduced in the hippocampus DG. Furthermore, ephrin-A5-deficient mice exhibited altered distribution of EphA4 receptor in the vascular endothelial cells and increased narrower capillaries in the hippocampus DG. EphA/ephrin-A signaling thus plays crucial roles in the establishment and/or maintenance of the brain vascular system, as an essential constituent of the adult neurogenic niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Aging / genetics
  • Animals
  • Cell Proliferation
  • Cell Survival / genetics
  • Down-Regulation / genetics
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Ephrin-A5 / genetics*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology*
  • Neurogenesis / physiology*
  • Receptors, Eph Family / genetics
  • Receptors, Eph Family / metabolism


  • Ephrin-A5
  • Receptors, Eph Family