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Developmentally upregulated transcriptional elongation factor a like 3 suppresses axon regeneration after optic nerve
Agnieszka Lukomska1, Juhwan Kim1, Bruce A Rheaume1
1Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030, USA.
Abstract:
Projection neurons of the mammalian central nervous system (CNS) do not spontaneously regenerate axons which have been damaged by an injury or disease, often leaving patients with permanent disabilities that affect motor, cognitive, or sensory functions. Although several molecular targets which promote some extent of axon regeneration in animal models have been identified, the resulting recovery is very limited, and the molecular mechanisms underlying the axonal regenerative failure in the CNS are still poorly understood. One of the most studied targets for axon regeneration in the CNS is the mTOR pathway. A number of developmentally regulated genes also have been found to play a role in CNS axon regeneration. Here, we found that Transcriptional Elongation Factor A Like 3 (Tceal3), belonging to the Bex/Tceal transcriptional regulator family, which also modulates the mTOR pathway, is developmentally upregulated in retinal ganglion cell (RGCs) projection CNS neurons, and suppresses their capacity to regenerate axons after injury.
Insights
Central nervous system (CNS) neurons fail to regenerate damaged axons. Transcriptional Elongation Factor A Like 3 (Tceal3) is upregulated in retinal ganglion cells (RGCs) and suppresses axon regeneration after injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Mammalian central nervous system (CNS) projection neurons exhibit limited spontaneous axon regeneration following injury or disease.
- This regenerative failure leads to permanent motor, cognitive, and sensory deficits.
- While molecular targets like the mTOR pathway show potential, underlying mechanisms remain poorly understood.
Purpose of the Study:
- To investigate the role of Transcriptional Elongation Factor A Like 3 (Tceal3) in CNS axon regeneration.
- To determine if Tceal3 expression is developmentally regulated in projection neurons.
- To elucidate the impact of Tceal3 on the regenerative capacity of retinal ganglion cells (RGCs) after injury.
Main Methods:
- Analysis of Tceal3 developmental expression in RGCs.
- Assessment of Tceal3's influence on RGC axon regeneration following experimental injury.
- Investigation of Tceal3's interaction with the mTOR pathway.
Main Results:
- Tceal3, a member of the Bex/Tceal family, is developmentally upregulated in RGC projection neurons.
- Upregulation of Tceal3 correlates with suppressed axon regeneration capacity in RGCs post-injury.
- Tceal3 modulates the mTOR pathway, a known factor in axon regeneration.
Conclusions:
- Tceal3 acts as a developmental suppressor of CNS axon regeneration in RGCs.
- Targeting Tceal3 may offer a novel therapeutic strategy to enhance CNS repair.
- Understanding Tceal3's role provides insights into the molecular basis of regenerative failure in the CNS.
