Related Experiment Videos
A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye
Sun-Yun Yu1, Soon Ji Yoo, Lihui Yang
1Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Abstract:
Regulated cell death and survival play important roles in neural development. Extracellular signals are presumed to regulate seven apparent caspases to determine the final structure of the nervous system. In the eye, the EGF receptor, Notch, and intact primary pigment and cone cells have been implicated in survival or death signals. An antibody raised against a peptide from human caspase 3 was used to investigate how extracellular signals controlled spatial patterning of cell death. The antibody crossreacted specifically with dying Drosophila cells and labelled the activated effector caspase Drice. It was found that the initiator caspase Dronc and the proapoptotic gene head involution defective were important for activation in vivo. Dronc may play roles in dying cells in addition to activating downstream effector caspases. Epistasis experiments ordered EGF receptor, Notch, and primary pigment and cone cells into a single pathway that affected caspase activity in pupal retina through hid and Inhibitor of Apoptosis Proteins. None of these extracellular signals appeared to act by initiating caspase activation independently of hid. Taken together, these findings indicate that in eye development spatial regulation of cell death and survival is integrated through a single intracellular pathway.
Insights
Extracellular signals regulate cell death and survival in neural development. This study reveals a single pathway integrating these signals in Drosophila eye development, involving EGF receptor, Notch, and specific cell types.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Regulated cell death and survival are crucial for neural development.
- Extracellular signals are known to influence caspases, enzymes involved in cell death.
- Specific pathways in eye development, including EGF receptor and Notch signaling, are implicated in cell fate decisions.
Purpose of the Study:
- To investigate how extracellular signals control the spatial patterning of cell death during eye development.
- To identify the specific caspases and genes involved in this process.
- To elucidate the integrated pathway linking extracellular signals to caspase activity.
Main Methods:
- Utilized an antibody against human caspase 3 to detect activated effector caspase Drice in dying Drosophila cells.
- Employed epistasis experiments to order genetic components within the cell death pathway.
- Investigated the roles of initiator caspase Dronc and the proapoptotic gene head involution defective (hid).
Main Results:
- The antibody specifically labeled activated Drice in dying Drosophila cells.
- Initiator caspase Dronc and the gene hid were essential for caspase activation in vivo.
- EGF receptor, Notch, primary pigment, and cone cells function in a single pathway affecting caspase activity via hid and Inhibitor of Apoptosis Proteins.
Conclusions:
- Spatial regulation of cell death and survival in eye development is integrated through a single intracellular pathway.
- Extracellular signals do not appear to initiate caspase activation independently of hid.
- Dronc may have roles beyond activating downstream caspases in dying cells.