A role of the fatiga oxygen sensor in Drosophila oogenesis

ACEVEDO JULIETA M; WAPPNER PABLO

Santa Cruz

Congreso; 5th International meeting of the Latin American Society for Developmental Biology; 2010

Latin American Society for Developmental Biology

In response to hypoxia cells, tissues and whole organisms induce the expression of a wide range of genes that tend to restore energy homeostasis. Hypoxic gene induction is mainly mediated by the Hypoxia Inducible Factor (HIF), a heterodimeric a/b transcription factor composed of two bHLH-PAS subunits. While HIF-βis constitutively expressed, HIF-α subunit is tightly regulated by oxygen. Oxygen regulation is mediated by specific Prolyl-4-hydroxilases (PHDs) that hydroxilate HIF-α in two proline residues utilizing O2 as a co substrate of the reaction. Hydroxilated HIF-α is targeted for degradation at the 26S proteasome. In our lab we have identified Sima and Fatiga (Fga) as the HIF-α and PHD fly homologues respectively. We have shown that whereas sima mutants are fully viable and fertile in normoxia, fga mutants are lethal at different developmental stages. We demonstrated that fga lethality is due to Sima over accumulation as fga-sima double mutants recover viability. Interestingly despite being fully viable fga-sima double mutants are sterile indicating that an alternative Fga target, different from Sima, is involved in the Drosophila ovary development. We have studied in detail the fga-sima ovary phenotype and found that mutant follicles are unable to carry out the transition from polyteny to poliploidy that occurs during normal Drosophila oogenesis. We found that over-activation of the transcription factor FOXO accounts for the ovary phenotype of the fga sima double mutants, since in fga-sima-foxo triple mutants ovaries were normal. Our results demonstrate that FOXO is regulated by Fga during Drosophila oogenesis.