Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells.

Ulrika Wilhelmsson, Isabell Lebkuechner, Renata Leke, Pavel Marasek, Xiaoguang Yang, Daniel Antfolk, Meng Chen, Paria Mohseni, Eva Lasič, Saša Trkov Bobnar, Matjaž Stenovec, Robert Zorec, Andras Nagy, Cecilia Sahlgren, Marcela Pekna, Milos Pekny

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14 Citations (Scopus)

Abstract

The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes-/-) mice. We found that the proliferation of Nes-/- neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes-/- mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.
Original languageUndefined/Unknown
Pages (from-to)4050–4066
JournalCerebral Cortex
Volume29
Issue number10
DOIs
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

Keywords

  • mouse
  • astrocytes
  • neural stem cells
  • nanofilaments
  • astrocyte motility
  • intermediate filaments
  • Nestin

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