Impaired hippocampal neurogenesis and vascular formation in ephrin-A5-deficient mice.
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.
Hara
Yoshinobu
Y
Division of Developmental Neuroscience, Core Center for Neuroscience, ART, Tohoku University School of Medicine, Sendai, Japan.
Nomura
Tadashi
T
Yoshizaki
Kaichi
K
Frisén
Jonas
J
Osumi
Noriko
N
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D036386:Ephrin-A5 / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D055495:Neurogenesis / Q000502:physiology*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism
D036386:Ephrin-A5; D036081:Receptors, Eph Family