During Drosophila oogenesis, the somatic follicle cells form an epithelial layer surrounding the germline cells to form egg chambers. In this process, follicle cell precursors are specified into polar cells, stalk cells, and main-body follicle cells. Proper specification of these three cell types ensures correct egg chamber formation and polarization of the anterior-posterior axis of the germline cells. Multiple signaling cascades coordinate to control the follicle cell fate determination, including Notch, JAK/STAT, and Hedgehog signaling pathways. Here, we show that the Hippo pathway also participates in polar cell specification. Over-activation of yorkie (yki) leads to egg chamber fusion, possibly through attenuation of polar cell specification. Loss-of-function experiments using RNAi knockdown or generation of mutant clones by mitotic recombination demonstrates that reduction of yki expression promotes polar cell formation in a cell-autonomous manner. Consistently, polar cells mutant for hippo (hpo) or warts (wts) are not properly specified, leading to egg chamber fusion. Furthermore, Notch activity is increased in yki mutant cells and reduction of Notch activity suppresses polar cell formation in yki mutant clones. These results demonstrate that yki represses polar cell fate through Notch signaling. Collectively, our data reveal that the Hippo pathway controls polar cell specification. Through repressing Notch activity, Yki serves as a key repressor in specifying polar cells during Drosophila oogenesis.

G72 is a schizophrenia-susceptible gene encoding a polypeptide with 153 amino acids. In 2002, it was originally proposed as an activator of D-amino acid oxidase (DAOA) that could enhance the activity of DAAO and subsequently reduce the neurotransmission of N-methyl-D-aspartate receptors. However, several controversial findings have been reported recently. Due to a number of inconsistent descriptions of pLG72's biofunctions, this study aims to identify the cellular effects induced by pLG72 in U87 cells using systems biology approaches. The analyses of transcriptomics and biological networks showed that pLG72 might be involved in the induction of oxidative stress. To confirm the in silico prediction, we tested and discovered that overexpression of pLG72 effectively enhanced reactive oxygen species (ROS) in U87 cells and, furthermore, this induction can be quenched by Tempol, a general ROS scavenger. Therefore, G72-transgenic mice presenting some psychiatric symptoms, along with the pLG72 level being significantly increased in the serum of patients with schizophrenia, have led us to propose that the ROS enhancement in mental diseases may be from the overexpression of pLG72 in brain cells.