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

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Abstract
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. Summary statement: We identified a novel role for Apontic as an important common regulator of the transcription of hedgehog and cyclin E. Our study provides important insights into the mechanism of organ development.

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