Ecrg4 deficiency extends the replicative capacity of neural stem cells in a Foxg1-dependent manner.
Development
; 146(4)2019 02 18.
Article
em En
| MEDLINE
| ID: mdl-30745428
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Regulação da Expressão Gênica no Desenvolvimento
/
Fatores de Transcrição Forkhead
/
Neurogênese
/
Células-Tronco Neurais
/
Proteínas de Neoplasias
/
Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article