Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid that activates the G protein-coupled receptors, LPA1-6, which are associated with a wide number of cellular responses including proliferation, migration, differentiation, and survival. Although LPA1-6 are expressed in the developing brain, their functions in brain development are not fully understood. In the present study, we analyzed the temporal expression pattern of LPA receptors (LPARs) during neocortical development and found that LPA2 is highly expressed in neural stem/progenitor cells (NS/PCs) in the embryonic neocortex. LPA2 activation on cultured NS/PCs using GRI977143, a selective LPA2 agonist, promoted neuronal differentiation. LPA2-induced neuronal expansion was inhibited by FR180204, an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, suggesting that LPA2 promotes neuronal differentiation via Erk1/2 signaling. In addition, LPA2 activation promotes neurite elongation and branch formation. These results suggest that LPA2 is a critical regulator of neuronal differentiation and development.
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