Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis.
The number of cells in an organ is regulated by mitogens and trophic factors that impinge on intrinsic determinants of proliferation and apoptosis. We here report the identification of an additional mechanism to control cell number in the brain: EphA7 induces ephrin-A2 reverse signaling, which negatively regulates neural progenitor cell proliferation. Cells in the neural stem cell niche in the adult brain proliferate more and have a shorter cell cycle in mice lacking ephrin-A2. The increased progenitor proliferation is accompanied by a higher number of cells in the olfactory bulb. Disrupting the interaction between ephrin-A2 and EphA7 in the adult brain of wild-type mice disinhibits proliferation and results in increased neurogenesis. The identification of ephrin-A2 and EphA7 as negative regulators of progenitor cell proliferation reveals a novel mechanism to control cell numbers in the brain.
Holmberg
Johan
J
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Armulik
Annika
A
Senti
Kirsten-André
KA
Edoff
Karin
K
Spalding
Kirsty
K
Momma
Stefan
S
Cassidy
Rob
R
Flanagan
John G
JG
Frisén
Jonas
J
D000818:Animals; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation; D036383:Ephrin-A2 / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009420:Nervous System / Q000166:cytology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
D036383:Ephrin-A2; D011994:Recombinant Proteins