TY - JOUR T1 - A Phosphatidylinositol Lipids System, Lamellipodin, and Ena/VASP Regulate Dynamic Morphology of Multipolar Migrating Cells in the Developing Cerebral Cortex JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11643 LP - 11656 DO - 10.1523/JNEUROSCI.0738-12.2012 VL - 32 IS - 34 AU - Satoshi Yoshinaga AU - Takahiro Ohkubo AU - Shinji Sasaki AU - Mutsuo Nuriya AU - Yukino Ogawa AU - Masato Yasui AU - Hidenori Tabata AU - Kazunori Nakajima Y1 - 2012/08/22 UR - http://www.jneurosci.org/content/32/34/11643.abstract N2 - In the developing mammalian cerebral cortex, excitatory neurons are generated in the ventricular zone (VZ) and subventricular zone; these neurons migrate toward the pial surface. The neurons generated in the VZ assume a multipolar morphology and remain in a narrow region called the multipolar cell accumulation zone (MAZ) for ∼24 h, in which they extend and retract multiple processes dynamically. They eventually extend an axon tangentially and begin radial migration using a migratory mode called locomotion. Despite the potential biological importance of the process movement of multipolar cells, the molecular mechanisms remain to be elucidated. Here, we observed that the processes of mouse multipolar cells were actin rich and morphologically resembled the filopodia and lamellipodia in growth cones; thus, we focused on the actin-remodeling proteins Lamellipodin (Lpd) and Ena/vasodilator-stimulated phosphoprotein (VASP). Lpd binds to phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] and recruits Ena/VASP, which promotes the assembly of actin filaments, to the plasma membranes. In situ hybridization and immunohistochemistry revealed that Lpd is expressed in multipolar cells in the MAZ. The functional silencing of either Lpd or Ena/VASP decreased the number of primary processes. Immunostaining and a Förster resonance energy transfer analysis revealed the subcellular localization of PI(3,4)P2 at the tips of the processes. A knockdown experiment and treatment with an inhibitor for Src homology 2-containing inositol phosphatase-2, a 5-phosphatase that produces PI(3,4)P2 from phosphatidylinositol (3,4,5)-triphosphate, decreased the number of primary processes. Our observations suggest that PI(3,4)P2, Lpd, and Ena/VASP are involved in the process movement of multipolar migrating cells. ER -