EphA receptors direct the differentiation of mammalian neural precursor cells through a mitogen-activated protein kinase-dependent pathway.
Ephrins are cell surface-associated ligands for Eph receptor tyrosine kinases and are implicated in repulsive axon guidance and cell migration. EphA2, 3, and 4 receptors and one of their cognate ligands, ephrin-A2, are expressed by cells in the subventricular zone and ganglionic eminence of the embryonic day 14.5 telencephalon and by neural precursor cells in vitro. Activation of EphA receptors in dissociated neural precursor cells in vitro facilitates the commitment to neuronal fates. The majority of ephrin-A1-induced neurons is immunoreactive for tyrosine hydroxylase. Blocking the signal by the extracellular domain of EphA in forebrain slices results in a decrease in neurogenesis. Extracellular signal-regulated kinase is activated by the ligand binding to EphA receptors and is involved in the neurogenesis through EphA receptors. Rap1, but not Ras, is activated in response to ephrin-A1. Our results identify EphA receptors as positive regulators of the mitogen-activated protein kinase pathway that exerts neurogenesis of neural precursor cells from the developing central nervous system.
Aoki
Miwa
M
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Yamashita
Toshihide
T
Tohyama
Masaya
M
D000818:Animals; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology; D003470:Culture Media; D036383:Ephrin-A2 / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008024:Ligands; D020935:MAP Kinase Signaling System; D051379:Mice; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D036081:Receptors, Eph Family / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D003470:Culture Media; D036383:Ephrin-A2; D008024:Ligands; D014443:Tyrosine; D012313:RNA; D014446:Tyrosine 3-Monooxygenase; D036081:Receptors, Eph Family; D020928:Mitogen-Activated Protein Kinases; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins