Endothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone.
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ABSTRACT:
SUBMITTER: Adams KL
PROVIDER: S-EPMC7195367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The largest diversity of neural lineages generated from the subventricular zone (SVZ) occurs early after birth and is regulated in a spatiotemporal manner depending on the expression of specific transcriptional cues. Transcriptomics and fate-mapping approaches were employed to explore the relationship between regional expression of transcription factors by neural stem cells (NSCs) and the specification of distinct neural lineages. Our results support an early priming of NSCs for the genesis of defined cell types depending on their spatial location in the SVZ and identify HOPX as a marker of a subpopulation primed toward astrocytic fates. Manipulation of HOPX expression, however, showed no effect on astrogenesis but resulted in marked changes in the number of NSCs and of their progenies. Taken together, our results highlight transcriptional and spatial heterogeneity of postnatal NSCs and reveal a key role for HOPX in controlling SVZ germinal activity.
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Project description:Parkinson's disease (PD) is associated with olfactory defects in addition to dopaminergic degeneration. Dopaminergic signalling is necessary for subventricular zone (SVZ) proliferation and olfactory bulb (OB) neurogenesis. Alpha-synuclein (α-syn or Snca) modulates dopaminergic neurotransmission, and SNCA mutations cause familial PD, but how α-syn and its mutations affect adult neurogenesis is unclear. To address this, we studied a bacterial artificial chromosome transgenic mouse expressing the A30P SNCA familial PD point mutation on an Snca-/- background. We confirmed that the SNCA-A30P transgene recapitulates endogenous α-syn expression patterns and levels by immunohistochemical detection of endogenous α-syn in a wild-type mouse and transgenic SNCA-A30P α-syn protein in the forebrain. The number of SVZ stem cells (BrdU+GFAP+) was decreased in SNCA-A30P mice, whereas proliferating (phospho-histone 3+) cells were decreased in Snca-/- and even more so in SNCA-A30P mice. Similarly, SNCA-A30P mice had fewer Mash1+ transit-amplifying SVZ progenitor cells but Snca-/- mice did not. These data suggest the A30P mutation aggravates the effect of Snca loss in the SVZ. Interestingly, calbindin+ and calretinin (CalR)+ periglomerular neurons were decreased in both Snca-/-, and SNCA-A30P mice but tyrosine hydroxylase+ periglomerular OB neurons were only decreased in Snca-/- mice. Cell death decreased in the OB granule layer of Snca-/- and SNCA-A30P mice. In the same region, CalR+ numbers increased in Snca-/- and SNCA-A30P mice. Thus, α-syn loss and human A30P SNCA decrease SVZ proliferation, cell death in the OB and differentially alter interneuron numbers. Similar disruptions in human neurogenesis may contribute to the olfactory deficits, which are observed in PD.
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Project description:Expression data of miRNAs from adult neural progenitor cells in subventricular zone after stroke. Genome-wide profilings of miRNAs were measured in cultured non-ischemic (N=3) and ischemic SVZ (N=3) neural progenitor cells using miRNA microarray.
2011-11-29 | E-GEOD-29287 | biostudies-arrayexpress
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