Dichaete, a Sox2 homologue, prevents activation of cell death in multiple developmental contexts

Abstract

ABSTRACTPrecisely regulated cell death plays a critical role in normal development and is controlled by the balance of pro-apoptotic and anti-apoptotic signals. In Drosophila, transcription of the clustered cell death activators grim and reaper is turned on in the developing nervous system to eliminate neural stem cells at the end of embryonic development. This transcription is activated by a pulse of the Hox gene abdominal-A. We show here that the Sox2 homologue Dichaete inhibits neural stem cell death when overexpressed, and loss of Dichaete promotes premature neural stem cell death. The anti-apoptotic activity of Dichaete opposes the pro-apoptotic factors abdominal-A, as well as the transcription factor grainyhead. The function of all three genes impinge on an enhancer that regulates the transcription of grim and reaper. Furthermore, we find that the balance between abdominal-A and Dichaete is likely to regulate the death of other cells during development, including cells in the developing midline, the developing hindgut, and in the early abdominal epidermis. Loss of Dichaete results in premature death in these tissues. This death can be rescued by the deletion of the enhancer region between grim and reaper. These data suggest that Dichaete functions to inhibit cell death activated by abdominal-A in multiple developmental contexts.