reduced cul-5 activity causes aberrant follicular morphogenesis and germ cell loss in drosophila oogenesiscul-5活动下降导致异常的滤泡形态发生和生殖细胞在果蝇卵子发生损失.pdfVIP

Reduced cul-5 Activity Causes Aberrant Follicular Morphogenesis and Germ Cell Loss in Drosophila Oogenesis 1¤ 1 1,2 Jan-Michael Kugler , Christopher Lem , Paul Lasko * ´ ´ ´ 1 Developmental Biology Research Initiative, Department of Biology, McGill University, Montreal, Quebec, Canada, 2 Goodman Cancer Centre, McGill University, Montreal, ´ Quebec, Canada Abstract Drosophila oogenesis is especially well suited for studying stem cell biology, cellular differentiation, and morphogenesis. The small modifier protein ubiquitin regulates many cellular pathways. Ubiquitin is conjugated to target proteins by a diverse class of enzymes called ubiquitin E3 ligases. Here we characterize the requirement of Cul-5, a key component of a subgroup of Cullin-RING-type ubiquitin E3 ligases, in Drosophila oogenesis. We find that reduced cul-5 activity causes the formation of aberrant follicles that are characterized by excess germ cells. We show that germ line cells overproliferate in cul-5 mutant females, causing the formation of abnormally large germ line cysts. Also, the follicular epithelium that normally encapsulates single germ line cysts develops aberrantly in cul-5 mutant, leading to defects in cyst formation. We additionally found that Cul-5 is required for germ cell maintenance, as germ cells are depleted in a substantial fraction of cul-5 mutant ovaries. All of these cul-5 phenotypes are strongly enhanced by reduced activity of gustavus (gus), which encodes a substrate receptor of Cul-5-based ubiquitin E3 ligases. Taken together, our results implicate Cul-5/Gus ubi