Apontic regulates cell proliferation and development by activating the expression of hedgehog and cyclin E

Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and development. Hyperactivation of hh and cyclin E has been linked to several types of cancer. However, transcriptional regulation of hh and cyclin E are not well understood. Here we show that an evolutionarily conserved transcription factor Apontic (Apt) is an activator of hh and cyclin E in Drosophila. Apt directly promotes the expression of hh and cyclin E through its binding site in the promoter regions of hh and cyclin E during wing development. This Apt-dependent proper expression of hh and cyclin E is required for cell proliferation and development of the wing. Apt-mediated expression of hh and cyclin E can direct proliferation of Hh-expressing cells and simultaneous growth, patterning and differentiation of Hh-recipient cells. The discovery of the coordinated expression of Hh and principal cell-cycle regulator Cyclin E by Apt implicates insight into the mechanism by which deregulated hh and cyclin E promotes tumor formation.