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

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 agedependent 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.

Ependymal cell maturation is heterogeneous and ongoing in the mouse spinal cord and dynamically regulated in response to injury

“…Differential expression analysis identified Ecrg4 and Mia as two of the most specific and highly expressed genes in ependymal cells (Figure 1D and Table S1). Both genes encode secreted factors that inhibit proliferation of neural stem cells (Gonzalez et al, 2011; Kujuro et al, 2010; Nakatani et al, 2019) and neuroectodermal tumour cells (Hau et al, 2002), respectively. We confirmed the ependymal-specific expression of Mia using RNAscope technology (Figure 1E).…”

Esophageal cancer-related gene 4 inhibits gastric cancer growth and metastasis by upregulating Krüppel-like factor 2 expression

“…Therefore, effective prognostic biomarkers for GC are urgently ECRG4 was first reported in 1998 by a team of researchers from Peking Union Medical College of China, who found that it was more upregulated in esophageal tumor-adjacent tissues compared with cancerous tissues (14). ECRG4 is reported to influence a variety of processes, including inflammatory response to injury (15,16), cardiovascular function (17), neural cell senescence, aging (18,19), stress (20), and articular chondrocyte differentiation (21). ECRG4 also works as a tumor repressor in various cancers, including esophageal, stomach, colorectal, and breast cancer (6,22,23).…”

The secreted protein augurin is a novel modulator of canonical Wnt signalling involved in osteoblast differentiation

“…It is possible, therefore, that alterations in bone and cartilage function may underlie the traits associated with the gene encoding augurin, both in mice and in humans. In addition, given the expression pattern of ECRG4 in many tissues under physiological conditions and its alterations in disease, the molecular function of augurin as a canonical Wnt signalling inhibitor may underpin several of its reported effects on cancer cell proliferation and tumour growth, 3,21 cell senescence, 22 stem cell renewal 2,23 and inflammation/response to tissue injury. 24,25…”