title: PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors.
abstract: Correct guidance of the migration of neural progenitor cells (NPCs) is essential for the development and repair of the central nervous system (CNS). Electric field (EF)-guided migration, electrotaxis, has been observed in many cell types. We report here that, in applied EFs of physiological magnitude, embryonic and adult NPCs show marked electrotaxis, which is dependent on the PI3K/Akt pathway. The electrotaxis was also evidenced by ex vivo investigation that transplanted NPCs migrated directionally towards cathode in organotypic spinal cord slice model when treated with EFs. Genetic disruption or pharmacological inhibition of phosphoinositide 3-kinase (PI3K) impaired electrotaxis, whereas EF exposure increased Akt phosphorylation in a growth factor-dependent manner and increased phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels. EF treatments also induced asymmetric redistribution of PIP3, growth factor receptors, and actin cytoskeleton. Electrotaxis in both embryonic and adult NPCs requires epidermal growth factor (EGF) and fibroblast growth factor (FGF). Our results demonstrate the importance of the PI3K/Akt pathway in directed migration of NPCs driven by EFs and growth factors and highlight the potential of EFs to enhance the guidance of various NPC populations in CNS repair therapies.
authors.affiliation: School of Dentistry, Cardiff Institute of Tissue Engineering & Repair, Cardiff University, Cardiff, CF14 4XY, UK.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Arocena
authors.affiliation: Institute of Molecular Biotechnology, Austrian Academy of Sciences, Dr. Bohr-Gasse, 1030 Vienna, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Penninger
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.affiliation: Institute for Regenerative Cures, UC Davis School of Medicine, 2921, Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: School of Dentistry, Cardiff Institute of Tissue Engineering & Repair, Cardiff University, Cardiff, CF14 4XY, UK.|School of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
authors.forename: Bing
authors.initials: B
authors.lastname: Song
mesh_terms: D000199:Actins / Q000378:metabolism; D053687:Adult Stem Cells / Q000187:drug effects* / Q000637:transplantation; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods*; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000637:transplantation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases