Pelota mediates gonocyte maturation and maintenance of spermatogonial stem cells in mouse testes

Abstract

Pelota (Pelo) is an evolutionarily conserved gene, and its deficiency in Drosophila affects both male and female fertility. In mice, genetic ablation of Pelo leads to embryonic lethality at the early implantation stage as a result of the impaired development of extra-embryonic endoderm (ExEn). To define the consequences of Pelo deletion on male germ cells, we temporally induced deletion of the gene at both embryonic and postnatal stages. Deletion of Pelo in adult mice resulted in a complete loss of whole-germ cell lineages after 45 days of deletion. The absence of newly emerging spermatogenic cycles in mutants confirmed that spermatogonial stem cells (SSCs) were unable to maintain spermatogenesis in the absence of PELO protein. However, germ cells beyond the undifferentiated SSC stage were capable of completing spermatogenesis and producing spermatozoa, even in the absence of PELO. Following the deletion of Pelo during embryonic development, we found that although PELO is dispensable for maintaining gonocytes, it is necessary for the transition of gonocytes to SSCs. Immunohistological and protein analyses revealed the attenuation of FOXO1 transcriptional activity, which induces the expression of many SSC self-renewal genes. The decreased transcriptional activity of FOXO1 in mutant testes was due to enhanced activity of the PI3K/AKT signaling pathway, which led to phosphorylation and cytoplasmic sequestration of FOXO1. These results suggest that PELO negatively regulates the PI3K/AKT pathway and that the enhanced activity of PI3K/AKT and subsequent FOXO1 inhibition are responsible for the impaired development of SSCs in mutant testes.

Conserved functions of human Pelota in mRNA quality control of nonstop mRNA

“…Pelota also controls the self‐renewal of germline stem cells , and regulates the development of extraembryonic endoderm and epidermal differentiation . Pelota mediates gonocyte maturation and maintenance of spermatogonial stem cells in mouse testes . Besides roles in the germline, Drosophila Pelota and Hbs1 are required for transposon silencing in the Drosophila germline , and for high efficiency viral replication .…”

Ribosome and Translational Control in Stem Cells

“…[134,135]. Interestingly, PELOTA is essential for mouse and drosophila GSC maintenance and spermatogenesis [136][137][138]. While dispensable for mouse ESC self-renewal, PELOTA is required for both extraembryonic endoderm differentiation and the reprogramming of iPSCs [139].…”

Pelota Regulates Epidermal Differentiation by Modulating BMP and PI3K/AKT Signaling Pathways

“…The generation of conditional Pelo-knockout (Pelo D/D ) mice was described elsewhere (Nyamsuren et al, 2014) To inactivate Pelo before the development of the skin barrier, pregnant Pelo F/F CreERT2 and control Pelo F/F mice were injected intraperitonally with Tam at embryonic stages E13.5 and E14.5, as described previously (Raju et al, 2015). To delete Pelo in 8-week-old Pelo F/F , Pelo F/þ CreERT2, and Pelo F/F CreERT2 mice, animals were injected with 1 mg of Tam for 5 consecutive days.…”

“…Deletion of Pelo in mice results in embryonic lethality at an early postimplantation stage (Adham et al, 2003). To circumvent the early embryonic lethality and to study the role of PELO during embryonic and postnatal life, we generated conditional knockout mice and investigated the effect of Pelo deletion on pluripotency and differentiation of embryonic stem cells and spermatogonial stem cells (Nyamsuren et al, 2014;Raju et al, 2015).…”