Related Experiment Video
Updated: Jul 8, 2026
Live-imaging of the Drosophila Pupal Eye
Published on: January 12, 2015
Control of cell cycle entry and exiting from the second mitotic wave in the Drosophila developing eye
1Ben May Department for Cancer Research, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. sukhanov@huggins.bsd.uchicago.edu
Background:
In the morphogenetic furrow (MF) of the Drosophila developing eye, all cells arrest in G1 and photoreceptor cell differentiation initiates. As the cells exit the MF, Notch signaling is required for the uncommitted cells to enter a synchronous round of cell division referred to as the "second mitotic wave" (SMW). How cell cycle entry and exit in SMW is regulated remains unclear. Recent studies have suggested that Notch signaling controls S phase in the SMW by regulating Cyclin A and the E2F transcription factor independent of Cyclin E. In this manuscript, we investigate the developmental regulation of cell cycle entry into and exit from SMW.
Results:
We demonstrate here that Cyclin E-dependent kinase activity is required for S phase entry in SMW. We show that removal of Su(H), a key transcription factor downstream of Notch signaling, blocks G1/S transition in SMW with strong upregulation of the Cyclin E/Cdk2 inhibitor Dacapo (Dap). We further show that the upregulation of Dap, which is mediated by bHLH protein Daughterless (Da), is important for cell cycle arrest of Su(H) mutant cells in SMW. Finally we show that removal of Dap leads to additional cell proliferation and an accumulation of the non-photoreceptor cells in the Drosophila developing eye.
Conclusion:
Our data demonstrate that Cyclin E/Cdk2 kinase activity is absolutely required for S phase in SMW, and that Dap is required for the proper cell cycle arrest of cells exiting the SMW. In addition, our results suggest that the G1 arrest of notch and Su(H) mutant cells in the SMW are regulated by distinct mechanisms, and that the upregulation of Dap contributes the G1 arrest of Su(H) mutant cells.
Insights
Cyclin E/Cdk2 kinase activity drives cell cycle entry in Drosophila eye development's second mitotic wave (SMW). Dacapo (Dap) is crucial for cell cycle arrest exiting SMW, particularly in Su(H) mutants.
Area of Science:
- Developmental Biology
- Cell Cycle Regulation
- Drosophila melanogaster research
Background:
- During Drosophila eye development, cells arrest in G1 within the morphogenetic furrow (MF), initiating photoreceptor differentiation.
- Notch signaling is essential for G1-arrested cells exiting the MF to enter the second mitotic wave (SMW) for a synchronous cell division.
- Regulation of cell cycle entry and exit during the SMW remains incompletely understood, with prior studies implicating Notch signaling in S phase control via Cyclin A and E2F, independent of Cyclin E.
Purpose of the Study:
- To investigate the developmental regulation of cell cycle entry into and exit from the second mitotic wave (SMW) in Drosophila eye development.
- To elucidate the role of Cyclin E-dependent kinase activity and downstream signaling pathways in SMW cell cycle dynamics.
Main Methods:
- Genetic manipulation of key cell cycle regulators and signaling pathway components in Drosophila melanogaster.
- Analysis of cell cycle progression, G1/S transition, and cell proliferation using mutant analysis.
- Investigating the role of Notch signaling, Suppressor of Hairless (Su(H)), Daughterless (Da), Dacapo (Dap), Cyclin E, and Cdk2 in SMW regulation.
Main Results:
- Cyclin E-dependent kinase activity is essential for S phase entry during the SMW.
- Loss of Su(H) function, a downstream mediator of Notch signaling, inhibits G1/S transition in the SMW and leads to significant upregulation of the Cyclin E/Cdk2 inhibitor Dacapo (Dap).
- Dap upregulation, influenced by the bHLH protein Daughterless (Da), is critical for the cell cycle arrest observed in Su(H) mutant cells within the SMW. Conversely, Dap removal results in increased proliferation and accumulation of non-photoreceptor cells.
Conclusions:
- Cyclin E/Cdk2 kinase activity is indispensable for S phase progression in the SMW.
- Dacapo (Dap) plays a vital role in ensuring proper cell cycle arrest as cells exit the SMW.
- The G1 arrest mechanisms for Notch and Su(H) mutant cells differ, with Dap upregulation contributing to the G1 arrest in Su(H) mutant cells.
Related Concept Videos
01:28The Cell Cycle Control System
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:11The Cell Cycle Control System
02:11The Cell Cycle Control System
02:15M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
01:27Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
02:39Positive Regulator Molecules