Tong Chao group’s new study published on Development uncovered that protein synthesis and degradation are critical to regulate germline stem cell homeostasis.

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.

Transgenic RNAi screening strategies in the fly testis and phenotype annotations of hits

Nine genes encoding ribosomal proteins contribute to both GSC self-renewal and TA-spermatogonia differentiation

Text link: http://dev.biologists.org/content/early/2016/07/27/dev.134247