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Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium.

ABSTRACT: The ventricular epithelium of the adult forebrain is a heterogeneous cell population that is a source of both quiescent and activated neural stem cells (qNSCs and aNSCs, respectively). We genetically targeted a subset of ventricle-contacting, glial fibrillary acidic protein (GFAP)-expressing cells, to study their involvement in qNSC/aNSC-mediated adult neurogenesis. Ventricle-contacting GFAP+ cells were lineage-traced beginning in early adulthood using adult brain electroporation and produced small numbers of olfactory bulb neuroblasts until at least 21 mo of age. Notably, electroporated GFAP+ neurogenic precursors were distinct from both qNSCs and aNSCs: they did not give rise to neurosphere-forming aNSCs in vivo or after extended passaging in vitro and they were not recruited during niche regeneration. GFAP+ cells with these properties included a FoxJ1+GFAP+ subset, as they were also present in an inducible FoxJ1 transgenic lineage-tracing model. Transiently overexpressing Mash1 increased the neurogenic output of electroporated GFAP+ cells in vivo, identifying them as a potentially recruitable population. We propose that the qNSC/aNSC lineage of the adult forebrain coexists with a distinct, minimally expanding subset of GFAP+ neurogenic precursors.

SUBMITTER: Joppe SE

PROVIDER: S-EPMC7266992 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium.

Joppé Sandra E SE Cochard Loïc M LM Levros Louis-Charles LC Hamilton Laura K LK Ameslon Pierre P Aumont Anne A Barnabé-Heider Fanie F Fernandes Karl Jl KJ

Life science alliance 20200601 7

The ventricular epithelium of the adult forebrain is a heterogeneous cell population that is a source of both quiescent and activated neural stem cells (qNSCs and aNSCs, respectively). We genetically targeted a subset of ventricle-contacting, glial fibrillary acidic protein (GFAP)-expressing cells, to study their involvement in qNSC/aNSC-mediated adult neurogenesis. Ventricle-contacting GFAP<sup>+</sup> cells were lineage-traced beginning in early adulthood using adult brain electroporation and ...[more]

PMID: 32482782

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Project description:We have explored the plastic ability of neuronal precursors to acquire different identities by manipulating their surrounding environment. Specifically, we sought to identify potential signals involved in the specification of forebrain dopaminergic neurons. Here we describe culture conditions under which tyrosine hydroxylase (TH) expression is induced in neuronal precursors, which were derived directly from the embryonic striatum and adult subependyma (SE) of the lateral ventricle or generated from multipotent forebrain stem cells. TH was successfully induced in all of these cell types by 24 hr exposure to basic fibroblast growth factor (FGF2) and glial cell conditioned media (CM). The greatest magnitude of the inductive action was on embryonic striatal precursors. Although FGF2 alone induced limited TH expression in striatal cells (1.1 +/- 0.2% of neurons), these actions were potentiated 17.5-fold (19.6 +/- 1.5% of neurons) when FGF2 was coadministered with B49 glial cell line CM. Of these TH-immunoreactive cells, approximately 15% incorporated bromodeoxyuridine (BrdU), indicating that they were newly generated, and 95% coexpressed the neurotransmitter GABA. To investigate whether precursors of the adult forebrain subependyma were competent to respond to the instructive actions of FGF2+CM, they were first labeled in vivo with a pulse of BrdU. Although none of the cells expressed TH in control, 0.2% of total cells showed TH immunoreactivity in FGF2+CM-treated cultures. Under these same conditions only, in vitro-generated precursors from epidermal growth factor-responsive stem cells exhibited TH expression in 10% of their total neuronal progeny. Regulation of neurotransmitter phenotype in forebrain neuronal precursors, by the synergistic action of FGF2 and glial-derived diffusible factors, may represent a first step in understanding how these cells are generated in the embryonic and adult brain and opens the prospect for their manipulation in vitro and in vivo for therapeutic use.

Dataset Information

Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium.

Publications

Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium.

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