Vrille (gene)

[2] Helene George and Regine Terracol discovered the first vrille alleles (vri1 and vri2) in 1997 by EMS-mutagenesis assay and found their products to be transcription factors involved in embryogenesis.

[3] Justin Blau elucidated additional "vrille" implications in 1999 while screening for clock-controlled genes in Drosophila heads that responded to PER/TIM heterodimers.

[7] Vrille acts as an enhancer of decapentaplegic (dpp) and easter, genes critical to the development of dorsal/ventral axis in the process of regional differentiation during Drosophila embryogenesis.

Easter is involved in initiating a protease cascade that activates the dorsal gene, resulting in repression of dpp in the ventral portion of the embryo during early fly development.

Overexpression of vri causes anti-proliferative effects in processes vital for limb generation, as well as abnormal phenotypes in salivary glands and internal organs.

The crustacean Daphnia magna co-opts its vri ortholog for activating the doublesex sex-determination gene, a task accomplished by tra in flies.

Interlocked molecular feedback loops in Drosophila melanogaster. CLOCK/CYCLE heterodimer acts as transcriptional activator (positive element) for period (per) and timeless (tim) genes. The heterodimer of PER/TIM is phosphorylated in the cytoplasm in the presence of specific kinases, and the phosphorylated complex then acts as inhibitor for its own transcription (negative element). The VRI and PDP1 proteins regulate the levels of CLK/CYC complex, which in turn are regulated by CLK/CYC. Thus, CLK/CYC heterodimer appears to be an important component that connects the two loops and is important for sustaining molecular oscillations. The protein Cryptochrome (CRY) has been implicated in the light entrainment pathways of the Drosophila molecular clock.