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Publication : Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone.

First Author  Genet N Year  2023
Journal  Cell Rep Volume  42
Issue  4 Pages  112371
PubMed ID  37043357 Mgi Jnum  J:335359
Mgi Id  MGI:7466029 Doi  10.1016/j.celrep.2023.112371
Citation  Genet N, et al. (2023) Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone. Cell Rep 42(4):112371
abstractText  The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by single-cell RNA sequencing and in vitro studies showing that ECs control NSC proliferation by regulating expression of genes associated with NSC quiescence and/or activation in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights inform adult NSC regulation and maintenance aimed at stem cell therapies for neurodegenerative disorders.
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