title: SDF1 regulates leading process branching and speed of migrating interneurons.
abstract: Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1 (stromal cell-derived factor-1) signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here, we demonstrate that SDF1 signaling reduces interneuron branching frequency by reducing cAMP levels via a G(i) signaling pathway using an in vitro mouse explant system, resulting in the maintenance of stream migration. Blocking SDF1 signaling or increasing branching frequency results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues.
authors.affiliation: Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Lysko
authors.forename: Mary
authors.initials: M
authors.lastname: Putt
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D049452:Green Fluorescent Proteins