Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors

Maor-Nof M, Romi E, Shalom HS, Ulisse V, Raanan C, Nof A, Leshkowitz D, Lang R, Yaron A (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Neuron Elsevier (Cell Press)

Book Volume: 92

Pages Range: 991-1006

Journal Issue: 5

DOI: 10.1016/j.neuron.2016.10.061

Abstract

Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription factor p53 and antagonizes the expression of the pro-degenerative factor, Puma (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16 protected axons from rapid degeneration and specifically reversed axonal innervation loss early in development with no effect on neuronal deficits. Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor.

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Weizmann Institute of Science IL Israel (IL)

How to cite

APA:

Maor-Nof, M., Romi, E., Shalom, H.S., Ulisse, V., Raanan, C., Nof, A.,... Yaron, A. (2016). Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors. Neuron, 92(5), 991-1006. https://dx.doi.org/10.1016/j.neuron.2016.10.061

MLA:

Maor-Nof, Maya, et al. "Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors." Neuron 92.5 (2016): 991-1006.

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