Investigation of linkers between the Notch pathway and endocycle regulators in Drosophila oogenesis. C. Althauser , W.M. Deng , H. Ruohola-Baker. Biochem, Univ Washington, Seattle, WA.

   During Drosophila oogenesis, the follicle cells undergo a switch from normal cell cycle to endocycle at stage six, whereby the M and G1 phases are bypassed, and the cells become polyploid. We have shown that Delta signaling from the germline to Notch in the follicle cells regulates this switch. We have also shown that String, a Cdc25 phosphatase that regulates the G2/M transition, is a downstream target of Notch and the transcription factor Suppressor of Hairless (Su(H)). Yet, because it has been found that cells in string mutant embryos arrest at the G2/M boundary and do not enter S phase, there are likely other components involved in regulating this endocycle switch. Previous studies have shown evidence that a rise and then drop in Cyclin E expression drives the transition between G1 and S phase, indicating this possible importance of Cyclin E expression in pushing the cell cycle from G2 to S phase during the switch to endocycle. It has recently been shown that the F-box protein, Archipelago (Ago), binds to Cyclin E, targeting it for ubiquitin-mediated degradation. Also, SEL-10 (the nematode and mouse counterpart of hCdc4/Fb27/Ago) is implicated in the control of signaling pathways involving Notch. We show that ago mutant follicle cell clones past stage six stain for the G2/M marker, Cyclin B, suggesting that Archipelago plays a role in regulating the switch to endocycle. Because the mutant cells do not stain for the mitotic marker, Phosphohistone-3, they apparently arrest in a G2 state. We are now testing if Ago is a linker between the Notch pathway and endocycle regulation.