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p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation
Neuronal migration is one of the fundamental processes during brain development. Several neurodevelopmental disorders can be traced back to dysregulated migration. Although substantial efforts have been placed in identifying molecular signals that stimulate migration, little is known about potential...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427104/ https://www.ncbi.nlm.nih.gov/pubmed/36040414 http://dx.doi.org/10.7554/eLife.79934 |
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author | Zanin, Juan P Friedman, Wilma J |
author_facet | Zanin, Juan P Friedman, Wilma J |
author_sort | Zanin, Juan P |
collection | PubMed |
description | Neuronal migration is one of the fundamental processes during brain development. Several neurodevelopmental disorders can be traced back to dysregulated migration. Although substantial efforts have been placed in identifying molecular signals that stimulate migration, little is known about potential mechanisms that restrict migration. These restrictive mechanisms are essential for proper development since it helps coordinate the timing for each neuronal population to arrive and establish proper connections. Moreover, preventing migration away from a proliferative niche is necessary in maintaining a pool of proliferating cells until the proper number of neuronal progenitors is attained. Here, using mice and rats, we identify an anti-migratory role for the p75 neurotrophin receptor (p75NTR) in cerebellar development. Our results show that granule cell precursors (GCPs) robustly express p75NTR in the external granule layer (EGL) when they are proliferating during postnatal development, however, they do not express p75NTR when they migrate either from the rhombic lip during embryonic development or from the EGL during postnatal development. We show that p75NTR prevented GCP migration by maintaining elevated levels of active RhoA. The expression of p75NTR was sufficient to prevent the migration of the granule cells even in the presence of BDNF (brain-derived neurotrophic factor), a well-established chemotactic signal for this cell population. Our findings suggest that the expression of p75NTR might be a critical signal that stops and maintains the GCPs in the proliferative niche of the EGL, by promoting the clonal expansion of cerebellar granule neurons. |
format | Online Article Text |
id | pubmed-9427104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-94271042022-08-31 p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation Zanin, Juan P Friedman, Wilma J eLife Developmental Biology Neuronal migration is one of the fundamental processes during brain development. Several neurodevelopmental disorders can be traced back to dysregulated migration. Although substantial efforts have been placed in identifying molecular signals that stimulate migration, little is known about potential mechanisms that restrict migration. These restrictive mechanisms are essential for proper development since it helps coordinate the timing for each neuronal population to arrive and establish proper connections. Moreover, preventing migration away from a proliferative niche is necessary in maintaining a pool of proliferating cells until the proper number of neuronal progenitors is attained. Here, using mice and rats, we identify an anti-migratory role for the p75 neurotrophin receptor (p75NTR) in cerebellar development. Our results show that granule cell precursors (GCPs) robustly express p75NTR in the external granule layer (EGL) when they are proliferating during postnatal development, however, they do not express p75NTR when they migrate either from the rhombic lip during embryonic development or from the EGL during postnatal development. We show that p75NTR prevented GCP migration by maintaining elevated levels of active RhoA. The expression of p75NTR was sufficient to prevent the migration of the granule cells even in the presence of BDNF (brain-derived neurotrophic factor), a well-established chemotactic signal for this cell population. Our findings suggest that the expression of p75NTR might be a critical signal that stops and maintains the GCPs in the proliferative niche of the EGL, by promoting the clonal expansion of cerebellar granule neurons. eLife Sciences Publications, Ltd 2022-08-30 /pmc/articles/PMC9427104/ /pubmed/36040414 http://dx.doi.org/10.7554/eLife.79934 Text en © 2022, Zanin and Friedman https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Zanin, Juan P Friedman, Wilma J p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title | p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title_full | p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title_fullStr | p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title_full_unstemmed | p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title_short | p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation |
title_sort | p75ntr prevents the onset of cerebellar granule cell migration via rhoa activation |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427104/ https://www.ncbi.nlm.nih.gov/pubmed/36040414 http://dx.doi.org/10.7554/eLife.79934 |
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