Necrosensor: a genetically encoded fluorescent sensor for visualizing necrosis in Drosophila.

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Necrosis was historically viewed as a passive cell death process. Recent discoveries of programmed necrosis (necroptosis) highlight its active regulation.
• Detecting necrosis in vivo has been difficult due to the absence of specific genetic biosensors, unlike those available for apoptosis.

Purpose of the Study:

• To develop a genetically encoded fluorescent sensor for reliable in vivo detection of necrosis.
• To utilize this sensor to investigate physiological necrosis during development and in response to stress.

Main Methods:

• Development of Necrosensor, a genetically encoded fluorescent sensor in Drosophila.
• Necrosensor utilizes High Mobility Group Box 1 (HMGB1), a damage-associated molecular pattern (DAMP), released during necrosis.
• Application of Necrosensor in various tissues under different stress conditions and during physiological processes like spermatogenesis.

Main Results:

• Necrosensor successfully detected necrosis induced by diverse stresses in multiple Drosophila tissues, in both live and fixed samples.
• The sensor identified physiological necrosis during spermatogenesis.
• A previously unknown physiological necrosis of hemocyte progenitors in the hematopoietic lymph gland was discovered using Necrosensor.

Conclusions:

• Necrosensor provides a novel transgenic system for real-time, in vivo detection of necrosis without invasive procedures.
• This tool facilitates the study of programmed necrosis and the discovery of new physiological cell death events.
• The findings advance our understanding of necrosis as a regulated biological process.