title: The transcription factor Fezf2 directs the differentiation of neural stem cells in the subventricular zone toward a cortical phenotype.
abstract: Postnatal neurogenesis in mammals is confined to restricted brain regions, including the subventricular zone (SVZ). In rodents, the SVZ is a lifelong source of new neurons fated to migrate to the olfactory bulb (OB), where the majority become GABAergic interneurons. The plastic capacity of neonatal and adult SVZ stem/progenitor cells is still largely unknown. By overexpressing the transcription factor Fezf2, a powerful master gene specifying the phenotype of glutamatergic subcerebral projecting neurons, we investigated whether the fate of postnatally generated SVZ neurons can be altered. Following lentiviral delivery of Fezf2 in the neonatal and adult SVZ niche, we showed that ectopic Fezf2 expression is sufficient to redirect the fate of SVZ stem cells. Thus, based on in vivo and in vitro experiments, we provide evidence that numerous Fezf2-positive OB neurons expressed glutamatergic pyramidal cell molecular markers instead of developing a GABAergic identity. Overexpression of Fezf2 had no effect on transit-amplifying progenitors or neuroblasts but was restricted to neural stem cells. Fezf2-respecified neurons bore features of pyramidal cells, exhibiting a larger cell body and a more elaborate dendritic tree, compared with OB granule cells. Patch-clamp recordings further indicated that Fezf2-respecified neurons had synaptic properties and a firing pattern reminiscent of a pyramidal cell-like phenotype. Together, the results demonstrate that neonatal and adult SVZ stem cells retain neuronal fate plasticity.
authors.affiliation: Department of Clinical Neurobiology, University Hospital and German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.affiliation: Department of Clinical Neurobiology, University Hospital and German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Corentin
authors.initials: C
authors.lastname: Le Magueresse
authors.affiliation: Department of Clinical Neurobiology, University Hospital and German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Clinical Neurobiology, University Hospital and German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Neitz
authors.affiliation: Department of Clinical Neurobiology, University Hospital and German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany h.monyer@dkfz-heidelberg.de.
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000166:cytology*; D002552:Cerebral Ventricles / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D005971:Glutamates; D009419:Nerve Tissue Proteins; C412364:Zfp312 protein, mouse
keywords: adult stem cell plasticity; respecification