Dataset Information

Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9.

ABSTRACT: Neural stem cell populations generate a wide spectrum of neuronal and glial cell types in a highly ordered fashion. MicroRNAs are essential regulators of this process. T-UCstem1 is a long non-coding RNA containing an ultraconserved element, and in vitro analyses in pluripotent stem cells provided evidence that it regulates the balance between proliferation and differentiation. Here we investigate the in vivo function of T-UCstem1. We show that T-UCstem1 is expressed in the forebrain neurogenic lineage that generates interneurons for the postnatal olfactory bulb. Gain of function in neural stem cells increased progenitor proliferation at the expense of neuron production, whereas knockdown had the opposite effect. This regulatory function is mediated by its interaction with miR-9-3p and miR-9-5p. Based thereon, we propose a mechanistic model for the role of T-UCstem1 in the dynamic regulation of neural progenitor proliferation during neurogenesis.

SUBMITTER: Pascale E

PROVIDER: S-EPMC7562942 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9.

Pascale Emilia E Beclin Christophe C Fiorenzano Alessandro A Andolfi Gennaro G Erni Andrea A De Falco Sandro S Minchiotti Gabriella G Cremer Harold H Fico Annalisa A

Stem cell reports 20200924 4

Neural stem cell populations generate a wide spectrum of neuronal and glial cell types in a highly ordered fashion. MicroRNAs are essential regulators of this process. T-UCstem1 is a long non-coding RNA containing an ultraconserved element, and in vitro analyses in pluripotent stem cells provided evidence that it regulates the balance between proliferation and differentiation. Here we investigate the in vivo function of T-UCstem1. We show that T-UCstem1 is expressed in the forebrain neurogenic l ...[more]

PMID: 32976763

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Project description:Neuronal activity has been identified as a key regulator of neuronal network development, but the impact of activity on migration and terminal positioning of interneuron subtypes is poorly understood. The absence of early subpopulation markers and the presence of intermingled migratory and postmigratory neurons make the developing cerebral cortex a difficult model to answer these questions. Postnatal neurogenesis in the subventricular zone (SVZ) offers a more accessible and compartmentalized model. Neural stem cells regionalized along the border of the lateral ventricle produce two main subtypes of neural progenitors, granule cells and periglomerular neurons that migrate tangentially in the rostral migratory stream (RMS) before migrating radially in the olfactory bulb (OB) layers. Here, we used targeted postnatal electroporation to compare the migration of these two populations in male and female mice. We do not observe any obvious differences regarding the mode of tangential or radial migration between these two subtypes. However, we find a striking increase of intrinsic calcium activity in granule cell precursors (GC-Ps) when they switch from tangential to radial migration. By decreasing neuronal excitability in GC-Ps, we find that neuronal activity has little effect on migration but is required for normal positioning and survival of GC-Ps in the OB layers. Strikingly, decreasing activity of periglomerular neuron precursors (PGN-Ps) did not impact their positioning or survival. Altogether these findings suggest that neuronal excitability plays a subtype specific role during the late stage of migration of postnatally born OB interneurons.SIGNIFICANCE STATEMENT While neuronal activity is a critical factor regulating different aspects of neurogenesis, it has been challenging to study its role during the migration of different neuronal subpopulations. Here, we use postnatal targeted electroporation to label and manipulate the two main olfactory bulb (OB) interneuron subpopulations during their migration: granule cell and periglomerular neuron precursors (PGN-Ps). We find a very striking increase of calcium activity only in granule cell precursors (GC-Ps) when they switch from tangential to radial migration. Interestingly, blocking activity in GC-Ps affected mainly their positioning and survival while PGN-Ps were not affected. These results suggest that neuronal activity is required specifically for the recruitment of GC-Ps in the OB layers.

Dataset Information

Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9.

Publications

Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9.

Similar Datasets

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