title: Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without causing uniform migration defects.
abstract: Neuronal precursors, generated throughout life in the subventricular zone, migrate through the rostral migratory stream to the olfactory bulb where they differentiate into interneurons. We found that the PI3K-Akt-mTorc1 pathway is selectively inactivated in migrating neuroblasts in the subventricular zone and rostral migratory stream, and activated when these cells reach the olfactory bulb. Postnatal deletion of Pten caused aberrant activation of the PI3K-Akt-mTorc1 pathway and an enlarged subventricular zone and rostral migratory stream. This expansion was caused by premature termination of migration and differentiation of neuroblasts and was rescued by inhibition of mTorc1. This phenotype is reminiscent of lamination defects caused by Pten deletion in developing brain that were previously described as defective migration. However, live imaging in acute slices showed that Pten deletion did not cause a uniform defect in the mechanics of directional neuroblast migration. Instead, a subpopulation of Pten-null neuroblasts showed minimal movement and altered morphology associated with differentiation, whereas the remainder showed unimpeded directional migration towards the olfactory bulb. Therefore, migration defects of Pten-null neurons might be secondary to ectopic differentiation.
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Zhu
authors.forename: Lionel M L
authors.initials: LM
authors.lastname: Chow
authors.forename: Ildar T
authors.initials: IT
authors.lastname: Bayazitov
authors.forename: Yiai
authors.initials: Y
authors.lastname: Tong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
authors.forename: David J
authors.initials: DJ
authors.lastname: Solecki
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Baker
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D018274:Electroporation; D066298:In Vitro Techniques; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse