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Drebrin controls neuronal migration through the formation and alignment of the leading process
Formation of a functional nervous system requires neurons to migrate to the correct place within the developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cyto...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356577/ https://www.ncbi.nlm.nih.gov/pubmed/22306864 http://dx.doi.org/10.1016/j.mcn.2012.01.006 |
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author | Dun, Xin-peng Bandeira de Lima, Tiago Allen, James Geraldo, Sara Gordon-Weeks, Phillip Chilton, John K. |
author_facet | Dun, Xin-peng Bandeira de Lima, Tiago Allen, James Geraldo, Sara Gordon-Weeks, Phillip Chilton, John K. |
author_sort | Dun, Xin-peng |
collection | PubMed |
description | Formation of a functional nervous system requires neurons to migrate to the correct place within the developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cytoskeletal changes to produce and guide leading process growth is unknown. One such cytoskeletal modulator is drebrin, an actin-binding protein known to induce protrusions in many cell types and be important for regulating neuronal morphology. Using the migration of oculomotor neurons as a model, we have shown that drebrin is necessary for the generation and guidance of the leading process. In the absence of drebrin, leading processes are not formed and cells fail to migrate although axon growth and pathfinding appear grossly unaffected. Conversely, when levels of drebrin are elevated the leading processes turn away from their target and as a result the motor neuron cell bodies move along abnormal paths within the brain. The aberrant trajectories were highly reproducible suggesting that drebrin is required to interpret specific guidance cues. The axons and growth cones of these neurons display morphological changes, particularly increased branching and filopodial number but despite this they extend along normal developmental pathways. Collectively these results show that drebrin is initially necessary for the formation of a leading process and subsequently for this to respond to navigational signals and grow in the correct direction. Furthermore, we have shown that the actions of drebrin can be segregated within individual motor neurons to direct their migration independently of axon guidance. |
format | Online Article Text |
id | pubmed-3356577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33565772012-05-31 Drebrin controls neuronal migration through the formation and alignment of the leading process Dun, Xin-peng Bandeira de Lima, Tiago Allen, James Geraldo, Sara Gordon-Weeks, Phillip Chilton, John K. Mol Cell Neurosci Article Formation of a functional nervous system requires neurons to migrate to the correct place within the developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cytoskeletal changes to produce and guide leading process growth is unknown. One such cytoskeletal modulator is drebrin, an actin-binding protein known to induce protrusions in many cell types and be important for regulating neuronal morphology. Using the migration of oculomotor neurons as a model, we have shown that drebrin is necessary for the generation and guidance of the leading process. In the absence of drebrin, leading processes are not formed and cells fail to migrate although axon growth and pathfinding appear grossly unaffected. Conversely, when levels of drebrin are elevated the leading processes turn away from their target and as a result the motor neuron cell bodies move along abnormal paths within the brain. The aberrant trajectories were highly reproducible suggesting that drebrin is required to interpret specific guidance cues. The axons and growth cones of these neurons display morphological changes, particularly increased branching and filopodial number but despite this they extend along normal developmental pathways. Collectively these results show that drebrin is initially necessary for the formation of a leading process and subsequently for this to respond to navigational signals and grow in the correct direction. Furthermore, we have shown that the actions of drebrin can be segregated within individual motor neurons to direct their migration independently of axon guidance. Academic Press 2012-03 /pmc/articles/PMC3356577/ /pubmed/22306864 http://dx.doi.org/10.1016/j.mcn.2012.01.006 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Dun, Xin-peng Bandeira de Lima, Tiago Allen, James Geraldo, Sara Gordon-Weeks, Phillip Chilton, John K. Drebrin controls neuronal migration through the formation and alignment of the leading process |
title | Drebrin controls neuronal migration through the formation and alignment of the leading process |
title_full | Drebrin controls neuronal migration through the formation and alignment of the leading process |
title_fullStr | Drebrin controls neuronal migration through the formation and alignment of the leading process |
title_full_unstemmed | Drebrin controls neuronal migration through the formation and alignment of the leading process |
title_short | Drebrin controls neuronal migration through the formation and alignment of the leading process |
title_sort | drebrin controls neuronal migration through the formation and alignment of the leading process |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356577/ https://www.ncbi.nlm.nih.gov/pubmed/22306864 http://dx.doi.org/10.1016/j.mcn.2012.01.006 |
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