A novel mechanism for Emc transcriptional regulation of Notch-mediated proliferation in Drosophila. Carrie M. Spratford, Justin P. Kumar. Biology, Indiana University, Bloomington, IN.

   During development, proliferation rates within developing tissues must be great enough to produce organs of the appropriate size and cellular complexity. Within Drosophila imaginal discs, the non-basic helix-loop-helix (HLH) protein Extramacrochaetae (Emc) is required for normal proliferation. Notch activity appears to be required for both imaginal tissue growth as well as emc transcription. Using the MARCM technique we have been able to establish a link between the growth defects associated with emc null clones and Notch-induced proliferation. Our studies demonstrate that emc null clones, when generated in a wild-type background, are significantly smaller when compared to neutral clones. emc is not required for cell viability as null clones are able to grow in a Minute background. We also provide evidence that emc is not a regulator of apoptosis as null clones fail to grow when programmed cell death is blocked via expression of p35. We will provide evidence that emc mediates a significant portion of Notch-induced proliferation within imaginal discs and that loss of emc blocks the execution of the Notch signal. The mechanism for how Emc regulates cell proliferation is poorly understood. It is currently thought that Emc functions as a competitive inhibitor and interferes with the interaction of Daughterless (Da), which itself is implicated in cell proliferation, with members of the Achaete-Scute Complex (AS-C). The resulting Da-Emc heterodimer is presumed to be unable to bind to DNA due to the missing basic domain within Emc. Here we present data to support an alternate model in which Emc interacts directly with DNA thereby interfering with ability of the Da/AS-C complex to bind and modulate target genes. We will propose a new regulatory model for Emc and its vertebrate homologs, Id1-4. Overall, the data obtained reveals that Emc may utilize several transcriptional mechanisms to affect many developmental processes including cell proliferation.