Essential role of Plzf in maintenance of spermatogonial stem cells

Costoya, José A.; Hobbs, Robin M.; Barna, Maria; Cattoretti, Giorgio; Manova, Katia; Sukhwani, Meena; Orwig, Kyle E.; Wolgemuth, Debra J.; Pandolfi, Pier Paolo

doi:10.1038/ng1367

Cited by 853 publications

(800 citation statements)

References 33 publications

Supporting

Mentioning

766

Contrasting

Unclassified

Order By: Relevance

“…Instead of being involved in spermatogonial apoptosis, E2F1 was necessary for the maintenance of spermatogonial stem cell (SSC) pool in the successive rounds of adult spermatogenesis. The loss of the self‐renewing SSCs likely contributed to the progression of the E2F1 −/− phenotype, since gradually the proportion of SCO tubules increased in a similar fashion as in the Plzf −/− mouse testis where the SSC are lost (Costoya et al ., 2004). The observed reduction in the 2C cell population at P40 in the flow cytometry assay likely resulted from a loss of the diploid spermatogonial cell population.…”

Section: Discussionmentioning

confidence: 99%

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

View full text Add to dashboard Cite

SummaryCell cycle control during spermatogenesis is a highly complex process owing to the control of the mitotic expansion of the spermatogonial cell population and following meiosis, induction of DNA breaks during meiosis and the high levels of physiological germ‐cell apoptosis. We set out to study how E2F1, a key controller of cell cycle, apoptosis, and DNA damage responses, functions in the developing and adult testis. We first analyzed the expression pattern of E2f1 during post‐natal testis development using RNA in situ hybridization, which showed a differential expression pattern of E2f1 in the adult and juvenile mouse testes. To study the function of E2f1, we took advantage of the E2F1−/− mouse line, which was back‐crossed to C57Bl/6J genetic background. E2f1 loss led to a severe progressive testicular atrophy beginning at the age of 20 days. Spermatogonial apoptosis during the first wave of spermatogenesis was decreased. However, already in the first wave of spermatogenesis an extensive apoptosis of spermatocytes was observed. In the adult E2F1−/− testes, the atrophy due to loss of spermatocytes was further exacerbated by loss of spermatogonial stem cells. Surprisingly, only subtle changes in global gene expression array profiling were observed in E2F1−/− testis at PND20. To dissect the changes in each testicular cell type, an additional comparative analysis of the array data was performed making use of previously published data on transcriptomes of the individual testicular cell types. Taken together, our data indicate that E2F1 has a differential role during first wave of spermatogenesis and in the adult testis, which emphasizes the complex nature of cell cycle control in the developing testis.

show abstract

Section: Discussionmentioning

confidence: 99%

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To test whether spermatogonia in our mutant zebrafish testes had abnormal features as reported in mice, we examined the premeiotic spermatogonial populations by examining the expression of Plzf (also known as zfp145), which is known as an undifferentiated spermatogonia-specific transcription factor in the mouse testis and is used as a molecular marker of undifferentiated spermatogonia (Buaas et al, 2004;Costoya et al, 2004). In zebrafish, Plzf is also expressed in type A spermatogonia, defined as a single spermatogonium in a cyst, and early type B spermatogonia, which are spermatogonia within cysts of 8 or fewer spermatogonial cells (Ozaki et al, 2011).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Saito

Siegfried

Nüsslein‐Volhard

et al. 2011

Developmental Dynamics

View full text Add to dashboard Cite

We describe here the isolation and cytogenetic characterization of three meiotic prophase I mutants, denoted ietsugu (its), iesada (isa), and iemochi (imo), isolated by a novel N-ethyl-N-nitrosourea mutagenesis screen for adult zebrafish gonadogenesis. Histological examination and flow cytometry analysis of testes from these mutants showed that each contained neither spermatids nor sperm. Staining for Sycp3 and cleaved Caspase-3 and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) assay further revealed that its had defects at the onset of meiosis, and that isa and imo spermatocytes failed to progress past the zygotene stage with apoptosis occurring in the testicular somatic cells. Staining for phosphorylated histone H2AX showed that foci formation in leptotene spermatocytes was disrupted in isa and imo. Furthermore, in vitro differentiation experiments revealed the possibility that the defects and sterility associated with mutations were germ line autonomous. Our results thus indicate that each responsible gene is necessary for meiotic progression during spermatogenesis and for male fertility.

show abstract

“…Several knockouts targeting transcription factors have recently resulted in mice exhibiting a progressive loss of germ cells leading to adult infertility (Chen et al, 2005;Falender et al, 2005;Buaas et al, 2004;Costoya et al, 2004). One of these factors, Etv5 (Ets Variant Gene 5), belongs to the Pea3 group of the Ets family of proteins, which are characterized by a highly conserved DNA-binding ETS domain (Sharrocks et al, 1997).…”

Section: Etv5 and Other Transcription Factorsmentioning

confidence: 99%

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

Hofmann

2008

Molecular and Cellular Endocrinology

204

178

View full text Add to dashboard Cite

SummaryMammalian spermatogenesis is a complex process in which male germ-line stem cells develop to ultimately form spermatozoa. Spermatogonial stem cells, or SSCs, are found in the basal compartment of the seminiferous epithelium. They self-renew to maintain the pool of stem cells throughout life, or they differentiate to generate a large number of germ cells. A balance between SSC self-renewal and differentiation in the adult testis is therefore essential to maintain normal spermatogenesis and fertility. Maintenance and self-renewal are tightly regulated by extrinsic signals from the surrounding microenvironment, called the spermatogonial stem cell niche. By physically supporting the SSCs and providing them with growth factors, the Sertoli cell is the main component of the niche. In addition, adhesion molecules that connect the SSCs to the basement membrane and cellular components of the interstitium between the seminiferous tubules are important regulators of the niche function. This review mainly focuses on glial cell line-derived neurotrophic factor (Gdnf), which is produced by Sertoli cells to maintain SSCs self-renewal, and the downstream signaling pathways induced by this crucial growth factor. Interactions between Gdnf and other signaling pathways that maintain self-renewal, as well as the role of novel SSC-and Sertoli cell-specific transcription factors, are also discussed.

show abstract

Essential role of Plzf in maintenance of spermatogonial stem cells

Cited by 853 publications

References 33 publications

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

Contact Info

Product

Resources

About