Cargando…
Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity
Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. He...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724523/ https://www.ncbi.nlm.nih.gov/pubmed/30840538 http://dx.doi.org/10.1091/mbc.E18-06-0361 |
_version_ | 1783449013356331008 |
---|---|
author | Bott, C. J. Johnson, C. G. Yap, C. C. Dwyer, N. D. Litwa, K. A. Winckler, B. |
author_facet | Bott, C. J. Johnson, C. G. Yap, C. C. Dwyer, N. D. Litwa, K. A. Winckler, B. |
author_sort | Bott, C. J. |
collection | PubMed |
description | Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2–3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron’s response to Sema3a, particularly during early axon guidance. |
format | Online Article Text |
id | pubmed-6724523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67245232019-09-05 Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity Bott, C. J. Johnson, C. G. Yap, C. C. Dwyer, N. D. Litwa, K. A. Winckler, B. Mol Biol Cell Articles Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2–3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron’s response to Sema3a, particularly during early axon guidance. The American Society for Cell Biology 2019-05-01 /pmc/articles/PMC6724523/ /pubmed/30840538 http://dx.doi.org/10.1091/mbc.E18-06-0361 Text en © 2019 Bott et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Bott, C. J. Johnson, C. G. Yap, C. C. Dwyer, N. D. Litwa, K. A. Winckler, B. Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title_full | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title_fullStr | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title_full_unstemmed | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title_short | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
title_sort | nestin in immature embryonic neurons affects axon growth cone morphology and semaphorin3a sensitivity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724523/ https://www.ncbi.nlm.nih.gov/pubmed/30840538 http://dx.doi.org/10.1091/mbc.E18-06-0361 |
work_keys_str_mv | AT bottcj nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity AT johnsoncg nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity AT yapcc nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity AT dwyernd nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity AT litwaka nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity AT wincklerb nestininimmatureembryonicneuronsaffectsaxongrowthconemorphologyandsemaphorin3asensitivity |