| Abstract |
Hox genes code for a family of a homeodomain (HD) containing transcription factors that use TALE-HD containing factors Pbx/Exd and Meis/Hth to specify the development of the anterior-posterior (AP) axis of an organism. However, the absence of TALE-HD containing factors from specific tissues emphasizes the need to identify and validate new Hox cofactors. In Drosophila central nervous system (CNS), Hox execute segment-specific apoptosis of neural stem cells (neuroblasts-NBs) and neurons. In abdominal segments of larval CNS, Hox gene Abdominal-A (AbdA) mediates NB apoptosis with the help of Exd and bHLH factor Grainyhead (Grh) using a 717 bp apoptotic enhancer. In this study, we show that this enhancer is critical for abdominal NB apoptosis and relies on two separable set of DNA binding motifs responsible for its initiation and maintenance. Our results also show that AbdA and Grh interact through their highly conserved DNA binding domains, and the DNA binding specificity of AbdA-HD is important for it to interact with Grh and essential for it to execute NB apoptosis in CNS. We also establish that Grh is required for Hox-dependent NB apoptosis in Labial and Sex Combs Reduced (Scr) expressing regions of the CNS, and it can physically interact with all the Hox proteins in vitro. Our biochemical and functional data collectively support the idea that Grh can function as a Hox cofactor and help them carry out their in vivo roles during development.
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