View Program - 63rd Annual Drosophila Research Conference

Tissue homeostasis depends on replacement of injured and defective cells by proliferation of resident adult stem cells. Homeostasis declines with age, largely due to decreased stem cell function and/or number. The Drosophila ovary provides an outstanding model for investigating age effects on tissue homeostasis, as oogenesis depends upon a well-defined germline stem cell (GSC) population that sustains oocyte production for many weeks. Age-dependent declines of oocyte production are associated with decreased mitosis, not GSC loss. Strikingly, we discovered that the asymmetric mitoses of GSCs are specialized, wherein the nuclear envelope and nuclear lamina remain throughout mitosis. During these specialized mitoses, spindles are nucleated from centrosomes embedded in the retained NL. The mode of GSC mitosis raises questions about how the mitotic NL contributes to homeostasis. To this end, we have studied age effects on accumulation of mitotic NL components, finding that lamin-B and emerin levels decline with age. These observations support predictions that deterioration of mitotic NL integrity reduces mitotic division and oocyte production. Further support for this prediction comes from our studies of the role of Checkpoint kinase 2, a transducer kinase that becomes activated upon NL defects and elevated DNA damage in germ cells. Notably, loss of Chk2 prolongs oocyte production, delaying loss of egg laying by 15 days, suggesting that activation of Chk2 contributes to reduced fecundity of older females. Taken together, our studies provide new insights into age-dependent contributions of the NL to homeostasis of the ovary.

Effects of nuclear lamina aging on oogenesis