title: Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.
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.
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, United States.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Zanin
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Abercrombie
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, United States.
authors.forename: Wilma J
authors.identifier: 0000-0002-3638-3504
authors.initials: WJ
authors.lastname: Friedman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002531:Cerebellum / Q000196:embryology*; D051379:Mice; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
chemical_list: C000595808:NTF3 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C068313:Ngfr protein, rat
keywords: HDAC1; cell biology; cell proliferation; cerebellum development; mouse; neuroscience; neurotrophins; p75 neurotrophin receptor; proNT3; rat