title: Paracrine Wnt/β-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis.
abstract: Spermatogonial stem cells (SSCs) fuel the production of male germ cells but the mechanisms behind SSC self-renewal, proliferation, and differentiation are still poorly understood. Using the Wnt target gene Axin2 and genetic lineage-tracing experiments, we found that undifferentiated spermatogonia, comprising SSCs and transit amplifying progenitor cells, respond to Wnt/β-catenin signals. Genetic elimination of β-catenin indicates that Wnt/β-catenin signaling promotes the proliferation of these cells. Signaling is likely initiated by Wnt6, which is uniquely expressed by neighboring Sertoli cells, the only somatic cells in the seminiferous tubule that support germ cells and act as a niche for SSCs. Therefore, unlike other stem cell systems where Wnt/β-catenin signaling is implicated in self-renewal, the Wnt pathway in the testis specifically contributes to the proliferation of SSCs and progenitor cells.
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hinako M
authors.initials: HM
authors.lastname: Takase
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; rnusse@stanford.edu.
authors.forename: Roeland
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D008297:Male; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; C495267:CTNNB1 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C095936:Wnt6 protein, mouse; D051176:beta Catenin
keywords: Wnt; spermatogonia; stem cells; testis