title: CXCL12-mediated murine neural progenitor cell movement requires PI3Kβ activation.
abstract: The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain.
authors.forename: Borja L
authors.initials: BL
authors.lastname: Holgado
authors.forename: Laura
authors.initials: L
authors.lastname: Martínez-Muñoz
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Sánchez-Alcañiz
authors.forename: Pilar
authors.initials: P
authors.lastname: Lucas
authors.forename: Vicente
authors.initials: V
authors.lastname: Pérez-García
authors.forename: Gema
authors.initials: G
authors.lastname: Pérez
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Rodríguez-Frade
authors.forename: Marta
authors.initials: M
authors.lastname: Nieto
authors.forename: Oscar
authors.initials: O
authors.lastname: Marín
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Carrasco
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carrera
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez-Dolado
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D053612:Janus Kinases / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D050791:STAT Transcription Factors; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases; D053612:Janus Kinases