The Notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK signaling axis

摘要: Notch signaling controls a wide range of cell fate decisions during development and disease via synergistic interactions with other pathways. Here, through genome-wide genetic screen in Drosophila, we uncover highly complex Notch-dependent circuitry that profoundly affects proliferation consequently hyperplasia. We report novel relationship between either the non-receptor tyrosine kinases Src42A Src64B to promote hyperplasia tissue disorganization, which results cycle perturbation, JAK/STAT signal activation, differential regulation targets. Significantly, JNK pathway is responsible for majority phenotypes transcriptional changes downstream Notch-Src synergy. previously reported Notch-Mef2 also activates JNK, indicating there are commonalities within circuitry; however, current data indicate accesses significantly different fashion than Notch-Mef2.