Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes

The homeostasis of self-renewal and differentiation in stem cells is strictly controlled by intrinsic signals and their niche. We
conducted a large-scale RNA interference (RNAi) screen in Drosophila testes and identified 221 genes required for germline
stem cell (GSC) maintenance or differentiation. Knockdown of these genes in
transit-amplifying spermatogonia and cyst cells further revealed various
phenotypes. Complex analysis uncovered that many of the identified genes are
involved in key steps of protein synthesis and degradation. A group of genes
that are required for mRNA splicing and protein translation contributes to both
GSC self-renewal and early germ cell differentiation. Loss of genes in protein
degradation pathway in cyst cells leads to testis tumor with overproliferated germ
cells. Importantly, in the Cullin 4-Ring E3
ubiquitin ligase (CRL4) complex, we identified multiple proteins that are
critical to GSC self-renewal. pic/DDB1, the linker protein of CRL4, is not only
required for GSC self-renewal in flies but also for maintenance of
spermatogonial stem cells (SSCs) in mice.