Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor
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 a...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/16654 |
| _version_ | 1829097006264483840 |
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| author | Juan Pablo Zanin Elizabeth Abercrombie Wilma J Friedman |
| author_facet | Juan Pablo Zanin Elizabeth Abercrombie Wilma J Friedman |
| author_sort | Juan Pablo Zanin |
| collection | DOAJ |
| description | 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 (p75NTR) 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 p75NTR 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 p75NTR, GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits. |
| first_indexed | 2024-04-11T09:05:46Z |
| format | Article |
| id | doaj.art-1735f06d0be048ba86ef6a802dbbfdc8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:46Z |
| publishDate | 2016-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1735f06d0be048ba86ef6a802dbbfdc82022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.16654Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptorJuan Pablo Zanin0Elizabeth Abercrombie1Wilma J Friedman2https://orcid.org/0000-0002-3638-3504Department of Biological Sciences, Rutgers University, Newark, United StatesCenter for Molecular and Behavioral Neuroscience, Rutgers University, Newark, United StatesDepartment of Biological Sciences, Rutgers University, Newark, United StatesCerebellar 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 (p75NTR) 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 p75NTR 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 p75NTR, GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.https://elifesciences.org/articles/16654neurotrophinscell proliferationp75 neurotrophin receptorcerebellum developmentHDAC1proNT3 |
| spellingShingle | Juan Pablo Zanin Elizabeth Abercrombie Wilma J Friedman Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor eLife neurotrophins cell proliferation p75 neurotrophin receptor cerebellum development HDAC1 proNT3 |
| title | Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| title_full | Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| title_fullStr | Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| title_full_unstemmed | Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| title_short | Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| title_sort | proneurotrophin 3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor |
| topic | neurotrophins cell proliferation p75 neurotrophin receptor cerebellum development HDAC1 proNT3 |
| url | https://elifesciences.org/articles/16654 |
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