Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-G(i/o) pathway.
Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates cortical development. Here we examined how LPA influences the cell fate of cortical neuroblasts using a neurosphere culture system. We generated neurospheres in the presence of basic fibroblast growth factor (bFGF). Treatment with LPA throughout the culture period significantly reduced the number of cells in the neurospheres. When dissociated single cells derived from neurospheres were induced to differentiate by adherence on coverslips, the proportion of MAP2-positive neurons was higher in LPA-treated neurospheres than in those treated with bFGF alone, and the proportion of myelin basic protein-positive oligodendrocytes was lower. Consistent with this finding, LPA raised the ratio of beta-tubulin type III-positive young neurons and reduced the ratio of CD140a-positive oligodendrocyte precursors in neurospheres. These effects of LPA were inhibited by pretreatment of neurospheres with pertussis toxin or an LPA(1)-preferring antagonist, Ki16425. Moreover, LPA-induced enhancement of neuronal differentiation was not observed in neurospheres derived from lpa(1)-null mice. These results suggest that LPA promotes the commitment of neuroblasts to the neural lineage through the LPA(1)-G(i/o) pathway.
Fukushima
Nobuyuki
N
Molecular Neurobiology, Department of Life Sciences, School of Science and Engineering, Kinki University, Kowakae 3-4-1, Higashiosaka 577-8502, Japan. nfukushima@life.kindai.ac.jp
Shano
Shinya
S
Moriyama
Ryutaro
R
Chun
Jerold
J
D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D007555:Isoxazoles; D008246:Lysophospholipids; D011422:Propionates; D014404:Tubulin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D001973:Bromodeoxyuridine