{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:49:08Z","timestamp":1787021348811,"version":"build-2736575974"},"reference-count":49,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100006264","name":"RIKEN","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005946","name":"Hokkaido University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1242\/dev.168120","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T11:35:23Z","timestamp":1549884923000},"source":"Crossref","is-referenced-by-count":23,"title":["Ecrg4 deficiency extends the replicative capacity of neural stem cells in a Foxg1-dependent manner"],"prefix":"10.1242","volume":"146","author":[{"given":"Yuka","family":"Nakatani","sequence":"first","affiliation":[{"name":"Center for Life Science Technology 1 Division of Bio-Function Dynamics Imaging , , RIKEN, Kobe, Hyogo 650-0047 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kiyonari","sequence":"additional","affiliation":[{"name":"Center for Life Science Technology 2 Animal Resource Development Unit and Genetic Engineering Team , , RIKEN, Kobe, Hyogo 650-0047 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7755-2650","authenticated-orcid":false,"given":"Toru","family":"Kondo","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine 3 Division of Stem Cell Biology , , , Sapporo 060-0815 , Japan"},{"name":"Hokkaido University 3 Division of Stem Cell Biology , , , Sapporo 060-0815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"2024061300254790400_DEV168120C1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S0092-8674(00)80783-7","article-title":"Subventricular zone astrocytes are neural stem cells in the adult mammalian brain","volume":"97","author":"Doetsch","year":"1999","journal-title":"Cell"},{"key":"2024061300254790400_DEV168120C2","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.ceb.2008.09.008","article-title":"The cell biology of neural stem and progenitor cells and its significance for their proliferation versus differentiation during mammalian brain development","volume":"20","author":"Farkas","year":"2008","journal-title":"Curr. 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