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