Regulated Production of SnoN2 is a Feature of Testicular Differentiation
MICROSCOPY RESEARCH AND TECHNIQUE, vol.72, no.11, pp.833-844, 2009 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 72 Issue: 11
- Publication Date: 2009
- Doi Number: 10.1002/jemt.20739
- Journal Name: MICROSCOPY RESEARCH AND TECHNIQUE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.833-844
- Keywords: testis, spermatogenesis, development, SMAD, activin, TGF beta, Skil, GROWTH-FACTOR-BETA, UBIQUITIN-DEPENDENT DEGRADATION, RECEPTOR-TYPE-II, CELL-PROLIFERATION, TUMOR-SUPPRESSOR, SPERMATOGONIAL PROLIFERATION, GENE-EXPRESSION, SMAD PROTEINS, CDNA-CLONES, FYVE DOMAIN
- Akdeniz University Affiliated: No
Abstract
Transforming growth factor betas (TGF beta s) and activins are key regulators of male fertility, affecting somatic and germ cell proliferation and differentiation in the developing and adult testis. Several studies have shown that these ligands influence discrete developmental stages, suggesting that temporal expression of modifying factors may determine their specific signaling outcomes. Upon binding to cell surface receptors, TGF beta and activin signals are transduced intracellularly by the phosphorylation and nuclear accumulation of SMAD2 and SMAD3 transcription factors. The objective of this study was to determine the cellular localization of phosphorylated SMAD2/3 and the transcriptional repressor SnoN (Ski-like), a modifier of SMAD2/3 transcriptional activity, in mouse testes. Western blot established that only the smaller SnoN isoform, SnoN2, is produced in the testis. By immunohistochemistry, widespread phospho-SMAD2/3 distribution was observed in somatic and germ cells at all ages. In contrast, SnoN2 production was highly regulated, being detected only in gonocytes and interstitial cells at birth and in pachytene spermatocytes at puberty. In the adult, SnoN2 expression differed to that during the first wave, being ubiquitously expressed but exhibiting regulated nuclear localization. In another model of spermatogenic differentiation, the irradiated rat testis, widespread phospho-SMAD2/3 contrasted with restricted SnoN2 expression. SnoN2 was limited to interstitial cells, with reduced staining intensity observed associated with the timing of spermatogenesis resumption. We conclude that somatic and germ cells at all differentiation stages are actively transducing TGF beta superfamily signals but that responses to these ligands may be selectively modulated by controlled production and nuclear localization of SnoN2. Microsc. Res. Tech. 72:833-844, 2009. (C) 2009 Wiley-Liss, Inc.