Related Experiment Videos
Nerve growth factor and ceramides modulate cell death in the early developing inner ear
L M Frago1, Y León, E J de la Rosa
1Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Abstract:
Regulation of normal development involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. We have investigated the signalling mechanisms involved in regulation of the balance between cell proliferation and apoptotic cell death in the otic vesicle. The sphingomyelin pathway signals apoptosis for nerve growth factor upon binding to p75 receptors. It is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide. In the present study, we show that nerve growth factor stimulates sphingomyelin hydrolysis and the concomitant ceramide release in organotypic cultures of otic vesicles. Both nerve growth factor and ceramide induce apoptotic responses to a different extent. Ceramide-induced apoptosis was suppressed by insulin-like growth factor-I which is a strong promoter of cell growth and morphogenesis for the developing inner ear. In contrast, ceramide-1-phosphate protected the explants from apoptosis induced by serum withdrawal but did not antagonise ceramide-induced cell death. This study suggests that sphingomyelin-derived second messengers might be key modulators of programmed cell death during development.
Insights
Nerve growth factor and ceramide signaling regulate cell death in developing otic vesicles. Insulin-like growth factor-I counteracts ceramide-induced apoptosis, highlighting sphingomyelin pathway
Area of Science:
- Developmental Biology
- Cell Signaling
- Neuroscience
Background:
- Normal development relies on balancing cell division, differentiation, and death.
- The sphingomyelin pathway, initiated by ceramide, is known to signal apoptosis via nerve growth factor (NGF) and p75 receptors.
Purpose of the Study:
- To investigate signaling mechanisms regulating the balance between cell proliferation and apoptosis in the otic vesicle.
- To elucidate the role of the sphingomyelin pathway in otic vesicle development.
Main Methods:
- Organotypic cultures of otic vesicles were used.
- Stimulation with nerve growth factor (NGF) and ceramide.
- Assessment of apoptotic responses and the effects of insulin-like growth factor-I (IGF-I) and ceramide-1-phosphate.
Main Results:
- NGF stimulates sphingomyelin hydrolysis and ceramide release in otic vesicle cultures.
- Both NGF and ceramide induce apoptosis, with varying degrees.
- IGF-I suppressed ceramide-induced apoptosis.
- Ceramide-1-phosphate protected against serum withdrawal-induced apoptosis but not ceramide-induced cell death.
Conclusions:
- Sphingomyelin-derived second messengers, particularly ceramide, play a significant role in modulating programmed cell death during otic vesicle development.
- The balance between pro-apoptotic (ceramide) and pro-survival (IGF-I) signals is crucial for normal inner ear development.