The Drosophila CREB binding protein gene nejire is involved in multiple signaling and cell migration processes in follicle cells. Zhiqiang Shu, Dongyu Jia, Wu-Min Deng. Biological Science, Florida State University, Tallahassee, FL.

   Drosophila oogenesis encompasses some of the most fascinating biological changes at the cellular level, e.g. cell growth and migration. These cellular events are regulated spatially and temporally by multiple signaling pathways. Among these, the activation of Notch pathway induces a switch from the mitotic cycle to the endocycle in the somatic follicle cells. To understand how Notch activation is precisely regulated and interacts with other pathways, we employed an in vivo RNAi screen and identified nejire (nej), the Drosophila homolog of CREB binding protein gene. We found that nej knockdown (KD) follicle cells showed defects in the expression of Notch signaling markers Cut. Interestingly, nej-KD cells also showed defects in border cell migration and dorsal appendage formation. The role of nej in border cell migration is related to the JNK signaling because misexpression of puckered, a negative regulator of the JNK pathway, alleviated the nej-KD- induced border cell migration defect; whereas the involvement of nej in dorsal appendage formation is related to EGFR signaling, as revealed by downregulation of the EGFR target genes. We also observed an intriguing phenotype in follicle cells that cover the oocyte during stages 9-11. These nej-KD follicle cells appeared to have lost their epithelial morphology and undergone concerted migration to cover only the posterior end of the oocyte. This phenotype resembles that of epithelial-mesenchymal transition (EMT), a fundamental process that governs morphogenesis in multicellular organisms and is reactivated in a variety of diseases, especially in the progression of carcinoma and tumor metastasis. Our results indicated that nej regulates the expression of adhesion molecules, such as E-cadherin and Armadillo in this EMT-like process. In summary, our studies reveal the involvement of nej in multiple signaling pathways, and in cell migration in different follicle cell groups. Further studies on nej will determine how this gene integrates different signaling inputs and regulates complex cellular events such as migration and differentiation.