Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor

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Abstract

Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75^NTR) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75^NTR in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75^NTR, GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

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Juan Pablo Zanin

Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, United States

For correspondence
juanpablo.zanin@rutgers.edu

Competing interests
The authors declare that no competing interests exist.
Elizabeth Abercrombie

Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, United States

Competing interests
The authors declare that no competing interests exist.
Wilma J Friedman

Department of Biological Sciences, Rutgers University, Newark, United States

For correspondence
wilmaf@andromeda.rutgers.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3638-3504

Funding

National Institutes of Health (1R56NS094589)

Wilma J Friedman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal studies were conducted using the National Institutes of Health guidelines for the ethical treatment of animals with approval of the Rutgers Animal Care and Facilities Committee (protocols 15065 and 15066).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.