Multiple Mechanisms Modulate Distinct Cellular Susceptibilities toward Apoptosis in the Developing Drosophila Eye

• Mitotic cells are extremely sensitive to apoptotic signals
• Postmitotic, yet undifferentiated, cells require EGFR signaling for survival
• Photoreceptor neurons accumulate the apoptosis inhibitor Diap1 for survival
• Cullin-3 degrades Diap1 in undifferentiated cells

SummaryAlthough apoptosis is mechanistically well understood, a comprehensive understanding of how cells modulate their susceptibility toward apoptosis in a developing tissue is lacking. Here, we reveal striking dynamics in the apoptotic susceptibilities of different cell types in the Drosophila retina over a period of only 24 hr. Mitotic cells are extremely susceptible to apoptotic signals, while postmitotic cells have developed several strategies to promote survival. For example, photoreceptor neurons accumulate the inhibitor of apoptosis, Diap1. In unspecified cells, Cullin-3-mediated degradation keeps Diap1 levels low. These cells depend on EGFR signaling for survival. As development proceeds, developmentally older photoreceptors degrade Diap1, resulting in increased apoptosis susceptibility. Finally, R8 photoreceptors have very efficient survival mechanisms independent of EGFR or Diap1. These examples illustrate how complex cellular susceptibility toward apoptosis is regulated in a developing organ. Similar complexities may regulate apoptosis susceptibilities in mammalian development, and tumor cells may take advantage of it.

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