Reference - Detail
|Author||Kurabayashi N, Tanaka A, Nguyen MD, Sanada K.|
|Title||The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons.|
Newborn neurons in the developing neocortex undergo radial migration, a process that is coupled with their precise passage from multipolar to bipolar shape. The cell-extrinsic signals that govern this transition are, however, poorly understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes to the establishment of a bipolar shape in mouse migratory neurons through LPA receptor 4 (LPA4). LPA4 is robustly expressed in migratory neurons. LPA4-depleted neurons show impaired multipolar-to-bipolar transition and become arrested in their migration. Further, LPA4-mediated LPA signaling promotes formation of the pia-directed process in primary neurons overlaid on neocortical slices. In addition, LPA4 depletion is coupled with altered actin organization as well as with destabilization of the F-actin-binding protein filamin A (FlnA). Finally, overexpression of FlnA rescues the morphology and migration defects of LPA4-depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and radial migration of newborn cortical neurons via remodeling of the actin cytoskeleton.
|MeSH||3T3 Cells Animals Cell Line Cell Movement / genetics* Cell Polarity / genetics* Filamins / metabolism HEK293 Cells Homeodomain Proteins / metabolism Humans Lysophospholipids / metabolism* Mice Mice, Inbred ICR Neocortex / cytology* Neurogenesis / physiology Neurons / cytology* Nuclear Proteins / metabolism RNA Interference RNA, Small Interfering / genetics Receptors, Lysophosphatidic Acid / metabolism Receptors, Purinergic / genetics Receptors, Purinergic / metabolism* Repressor Proteins / metabolism Signal Transduction|
|DNA material||HA-LPA4/pCAGEN (RDB17289) HA-LPA4-res/pCAGEN (RDB17290) Lifeact-DsRed/pCAGEN (RDB17291) LPA4 shRNA#1/pBS-U6 (RDB17292) LPA4 shRNA#2/pBS-U6 (RDB17293)|