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Updated: Jun 8, 2026
Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
Differential roles of ERK1/2 and JNK in retinal development and degeneration
Maryanne Donovan1, Francesca Doonan, Thomas G Cotter
1Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland. ma.donovan@ucc.ie
Abstract:
Programmed cell death is well established as a key factor in the development of the vertebrate nervous system of which the retina is a unique sensory component. However, it is of utmost importance for the survival of post-mitotic tissues such as the retina that the execution of the cell death program is kept under stringent control once development is complete. This is exemplified by the many retinal dystrophies where aberrant apoptosis results in loss of distinct cell layers in the mature retina and often culminates in blindness. In this study, we report that the extracellular signal-regulated kinase (ERK1/2) pathway plays a key role in the regulation of apoptosis during retinal development. We show that as the retina matures, the emphasis shifts towards survival and ERK1/2 is activated resulting in phosphorylation of the potent BH3-only protein Bim(EL) and a dramatic decline in Bim(EL) expression via proteasomal degradation. We find that activation of ERK1/2 also occurs in response to injury in retinal explants. However, this is a transient response and appears to be overcome by Jun N-terminal kinase activation resulting in induction of Bim(EL) mRNA and photoreceptor apoptosis. Our findings provide new insights into the intracellular pathways responsible for regulating apoptosis during neuronal development and degeneration.
Insights
The extracellular signal-regulated kinase (ERK1/2) pathway controls programmed cell death in the developing retina. ERK1/2 activation promotes survival by degrading the Bim protein, preventing photoreceptor apoptosis.
Area of Science:
- Neuroscience
- Cell Biology
- Ophthalmology
Background:
- Programmed cell death (apoptosis) is crucial for vertebrate nervous system development, including the retina.
- Aberrant apoptosis in mature retinas leads to retinal dystrophies and blindness.
- Maintaining stringent control over apoptosis is vital for post-mitotic tissues like the retina.
Purpose of the Study:
- To investigate the role of the extracellular signal-regulated kinase (ERK1/2) pathway in regulating retinal apoptosis.
- To elucidate the molecular mechanisms by which ERK1/2 influences cell survival and death in the retina.
Main Methods:
- Analysis of ERK1/2 pathway activation during retinal development and in response to injury.
- Investigation of Bim(EL) protein expression and degradation.
- Assessment of Jun N-terminal kinase (JNK) activation and its effect on photoreceptor apoptosis.
Main Results:
- ERK1/2 pathway activation correlates with retinal maturation and promotes cell survival.
- Activated ERK1/2 leads to phosphorylation and proteasomal degradation of Bim(EL), reducing its expression.
- Retinal injury triggers a transient ERK1/2 response, which is overridden by JNK activation, inducing Bim(EL) and photoreceptor apoptosis.
Conclusions:
- The ERK1/2 pathway is a key regulator of apoptosis during retinal development and in response to injury.
- A shift towards survival signaling via ERK1/2-mediated Bim(EL) degradation is essential for mature retinal integrity.
- Dysregulation of these pathways, particularly JNK-induced Bim(EL) expression, contributes to photoreceptor degeneration.
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