The Role of DMyb in Programmed Neural Cell Death During Drosophila Development

The MYB-gene family encodes sequence-specific DNA-binding transcription factors that have been implicated in the regulation of both normal and neoplastic growth. The Drosophila Myb protein, DMyb (and vertebrate B-Myb protein), has been shown to be part of a large multi-subunit complex called the dREAM/MMB (Drosophila RBF, d E2F2, and DMyb-interacting proteins/ Myb-MuvB) complex, which has been implicated in the regulation of DNA replication and transcriptional regulation of a wide array of genes. Detailed phenotypic analysis of mutations in the Drosophila myb gene, Dm myb, has revealed a previously undiscovered function for DMyb and the dREAM/MMB complex in promoting programmed cell death (PCD) of specified sensory organ precursor (SOP) daughter cells. This function is achieved in cooperation with the pro-apoptotic protein Grim and found in at least two different settings in the peripheral nervous system (PNS). Unlike previously analyzed settings, in which the main role of DMyb has been to antagonize the activities of other dREAM/MMB complex members, it appears to be the critical effector in promoting PCD. The finding that Dm myb and grim are both involved in regulating PCD in two distinct settings suggests that these two genes may work together in additional contexts to mediate PCD.;In addition, Dm myb genetically interacts with several genes encoding components of the Notch signaling pathway in multiple developmental processes in wing development: the establishment of the wing dorsal/ventral (D/V) boundary and the refinement process of SOP cell selection at the anterior wing margin. Genetic analyses of mutations that modulate Notch signaling have indicated an antiapoptotic role for the signaling pathway in the neural precursor and glial cells at the posterior wing margin (PWM). As is the case during the establishment of the wing D/V boundary, DMyb function antagonizes Notch signaling in PWM neural precursor cells. Additionally, these analyses have further supported the notion that the presence of ectopic neurons at the PWM is indeed caused by reduced apoptotic responses in a specific precursor cell and not by mis-specification of SOP daughter cells. These results have pointed to a possible mechanism whereby DMyb regulates apoptotic decisions in the PNS: antagonizing the antiapoptotic Notch signaling pathway and promoting the proapoptotic activity of Grim, possibly via its effects on Notch signaling.