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The stabilization of β-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression

By Tohru Kimura, Toshinobu Nakamura, Kazushige Murayama, Hiroki Umehara, Noriko Yamano, Shoko Watanabe, Makoto M. Taketo and Toru Nakano

Abstract

AbstractPrimordial germ cells (PGCs) are germ cell precursors that are committed to sperm or oocytes. Dramatic proliferation during PGC development determines the number of founder spermatogonia and oocytes. Although specified to a germ lineage, PGCs produce pluripotent embryonic germ (EG) cells in vitro and testicular teratomas in vivo. Wnt/β-catenin signaling regulates pluripotency and differentiation in various stem cell systems, and dysregulation of this signaling causes various human cancers. Here, we examined the role of Wnt/β-catenin signaling in PGC development. In normal PGC development, Wnt/β-catenin signaling is suppressed by the GSK3β-mediated active degradation of β-catenin and the low expression of canonical Wnt molecules. The effects of aberrant activation of Wnt/β-catenin signaling in PGCs were analyzed using mice carrying a deletion of the exon that encodes the GSK3β phosphorylation sites in the β-catenin locus. Despite the potential activity of Wnt/β-catenin signaling in stem cell maintenance and carcinogenesis in various cell lineages, teratomas were not induced in the mice expressing the nuclear-localized β-catenin in PGCs. Instead, the mutant mice showed germ cell deficiency caused by the delayed cell cycle progression of the proliferative phase PGCs. Our results show that the suppression of Wnt/β-catenin signaling is a prerequisite for the normal development of PGCs

Publisher: Elsevier Inc.
Year: 2006
DOI identifier: 10.1016/j.ydbio.2006.06.038
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