DREF Is Required for Efficient Growth and Cell Cycle Progression in Drosophila Imaginal Discs

Abstract

Based on overexpression studies and target gene analyses, the transcription factor DNA replication-related element factor (DREF) has been proposed to regulate growth and replication in Drosophila melanogaster. Here we present loss-of-function experiments to analyze the contribution of DREF to these processes. RNA interference-mediated extinction of DREF function in vivo demonstrates a requirement for the protein for normal progression through the cell cycle and consequently for growth of imaginal discs and the derived adult organs. We show that DREF regulates the expression of genes that are required for the transition of imaginal disc cells through S phase. In conditions of suppressed apoptosis, DREF activation can cause overgrowth of developing organs. These data establish DREF as a global regulator of transcriptional programs that mediate cell proliferation and organ growth during animal development.

ACKNOWLEDGMENTS

This work was supported by NIH grant RO1 EY014624 to D.B.

We thank Christine Sommers for expert technical help and generation of transgenic fly lines and Katsuhito Ohno for fly stock carrying UAS DREF. Peter Keng and Tara Calcagni provided assistance in generating and interpreting FACS data.