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Development. 2019 Feb 18;146(4). pii: dev168120. doi: 10.1242/dev.168120.

Ecrg4 deficiency extends the replicative capacity of neural stem cells in a Foxg1-dependent manner.

Author information

1
Division of Bio-Function Dynamics Imaging, Center for Life Science Technology, RIKEN, Kobe, Hyogo 650-0047, Japan.
2
Animal Resource Development Unit and Genetic Engineering Team, Center for Life Science Technology, RIKEN, Kobe, Hyogo 650-0047, Japan.
3
Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan tkondo@igm.hokudai.ac.jp.

Abstract

The self-renewal activity of neural stem cells (NSCs) has been suggested to decrease with aging, resulting in age-dependent declines in brain function, such as presbyopia and memory loss. The molecular mechanisms underlying decreases in NSC proliferation with age need to be elucidated in more detail to develop treatments that promote brain function. We have previously reported that the expression of esophageal cancer-related gene 4 (Ecrg4) was upregulated in aged NSCs, whereas its overexpression decreased NSC proliferation, suggesting a functional relationship between Ecrg4 and NSC aging. Using Ecrg4-deficient mice in which the Ecrg4 locus was replaced with the lacZ gene, we here show that Ecrg4 deficiency recovered the age-dependent decline in NSC proliferation and enhanced spatial learning and memory in the Morris water-maze paradigm. We demonstrate that the proliferation of Ecrg4-deficient NSCs was partly maintained by the increased expression of Foxg1. Collectively, these results determine Ecrg4 as a NSC aging factor.

KEYWORDS:

Aging; Ecrg4; Foxg1; Memory; Neural stem cells (NSCs)

PMID:
30745428
DOI:
10.1242/dev.168120
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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