Developmental Biology Hindsight in the Switch from Mitotic Cycle to Endocycle

Nancy R. Gough

Science's STKE, AAAS, Washington, DC 20005, USA

Follicle cells of the Drosophila egg chamber undergo a switch from mitotic cell divisions to endoreplication in which the DNA is replicated but the cells do not divide. Notch signaling is known to be an important input into the switch. In addition, decreased function of two regulators of the M phase of the cell cycle, Cut and String, is also required for this transition. Sun and Deng show that Notch stimulates the accumulation (based on antibody staining) of a zinc finger transcription factor called Hindsight (Hnt) and that Hnt appears to mediate this switch in cell cycle programs. Cells in which Notch signaling was defective did not show the usual increase in Hnt at the stage that the endoreplication cycle normally occurs. Cells in which Hnt function was decreased or absent showed delayed exit from the mitotic cell cycle and increased abundance of Cut and String compared with adjacent wild-type cells in mosaic egg chambers. Furthermore, premature expression of Hnt caused the cells to enter the endoreplication cycle earlier than did wild-type cells, and misexpression of Hnt also decreased the abundance and activities of Cut and String. Hedgehog signaling is present in the stages when the follicle cells are undergoing mitotic cell divisions, and then signaling through this pathway is decreased as the cells enter the stage of endoreplication. Sun and Deng show that Notch signaling is necessary for this inhibition of Hedgehog signaling and that Hnt appears to mediate this pathway crosstalk. Cells in which Hnt was defective showed elevated levels of Cubitus interruptus (Ci), a marker for Hedgehog signaling, whereas Ci is completely undetected in cells in which Hnt is misexpressed prematurely. Thus, Hnt appears to carry the Notch signal that opposes Hedgehog signaling and allows endoreplication to occur.

J. Sun, W.-M. Deng, Hindsight mediates the role of Notch in suppressing Hedgehog signaling and cell proliferation. Dev. Cell 12, 431-442 (2007). [PubMed]