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

Yoshinobu Hara, Tadashi Nomura, Kaichi Yoshizaki, Jonas Frisén, Noriko Osumi

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)974-983
Number of pages10
JournalStem Cells
Issue number5
Publication statusPublished - 2010 May


  • Adult stem cells
  • Astrocytes
  • Neural stem cell
  • Stem cell-microenvironment interactions

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology


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