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Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase
The fundamental problem in axon growth and guidance is to understand how cytoplasmic signaling modulates the cytoskeleton to produce directed growth cone motility. We here dissect this process using live imaging of the TSM1 axon of the developing Drosophila wing. We find that the growth cone is almo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185889/ https://www.ncbi.nlm.nih.gov/pubmed/31967935 http://dx.doi.org/10.1091/mbc.E19-10-0563 |
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author | Clarke, Akanni McQueen, Philip G. Fang, Hsiao Yu Kannan, Ramakrishnan Wang, Victor McCreedy, Evan Buckley, Tyler Johannessen, Erika Wincovitch, Stephen Giniger, Edward |
author_facet | Clarke, Akanni McQueen, Philip G. Fang, Hsiao Yu Kannan, Ramakrishnan Wang, Victor McCreedy, Evan Buckley, Tyler Johannessen, Erika Wincovitch, Stephen Giniger, Edward |
author_sort | Clarke, Akanni |
collection | PubMed |
description | The fundamental problem in axon growth and guidance is to understand how cytoplasmic signaling modulates the cytoskeleton to produce directed growth cone motility. We here dissect this process using live imaging of the TSM1 axon of the developing Drosophila wing. We find that the growth cone is almost purely filopodial, and that it extends by a protrusive mode of growth. Quantitative analysis reveals two separate groups of growth cone properties that together account for growth cone structure and dynamics. The core morphological features of the growth cone are strongly correlated with one another and define two discrete morphs. Genetic manipulation of a critical mediator of axon guidance signaling, Abelson (Abl) tyrosine kinase, shows that while Abl weakly modulates the ratio of the two morphs it does not greatly change their properties. Rather, Abl primarily regulates the second group of properties, which report the organization and distribution of actin in the growth cone and are coupled to growth cone velocity. Other experiments dissect the nature of that regulation of actin organization and how it controls the spatial localization of filopodial dynamics and thus axon extension. Together, these observations suggest a novel, probabilistic mechanism by which Abl biases the stochastic fluctuations of growth cone actin to direct axon growth and guidance. |
format | Online Article Text |
id | pubmed-7185889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-71858892020-06-06 Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase Clarke, Akanni McQueen, Philip G. Fang, Hsiao Yu Kannan, Ramakrishnan Wang, Victor McCreedy, Evan Buckley, Tyler Johannessen, Erika Wincovitch, Stephen Giniger, Edward Mol Biol Cell Articles The fundamental problem in axon growth and guidance is to understand how cytoplasmic signaling modulates the cytoskeleton to produce directed growth cone motility. We here dissect this process using live imaging of the TSM1 axon of the developing Drosophila wing. We find that the growth cone is almost purely filopodial, and that it extends by a protrusive mode of growth. Quantitative analysis reveals two separate groups of growth cone properties that together account for growth cone structure and dynamics. The core morphological features of the growth cone are strongly correlated with one another and define two discrete morphs. Genetic manipulation of a critical mediator of axon guidance signaling, Abelson (Abl) tyrosine kinase, shows that while Abl weakly modulates the ratio of the two morphs it does not greatly change their properties. Rather, Abl primarily regulates the second group of properties, which report the organization and distribution of actin in the growth cone and are coupled to growth cone velocity. Other experiments dissect the nature of that regulation of actin organization and how it controls the spatial localization of filopodial dynamics and thus axon extension. Together, these observations suggest a novel, probabilistic mechanism by which Abl biases the stochastic fluctuations of growth cone actin to direct axon growth and guidance. The American Society for Cell Biology 2020-03-15 /pmc/articles/PMC7185889/ /pubmed/31967935 http://dx.doi.org/10.1091/mbc.E19-10-0563 Text en © 2020 Clarke 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 Clarke, Akanni McQueen, Philip G. Fang, Hsiao Yu Kannan, Ramakrishnan Wang, Victor McCreedy, Evan Buckley, Tyler Johannessen, Erika Wincovitch, Stephen Giniger, Edward Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title | Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title_full | Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title_fullStr | Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title_full_unstemmed | Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title_short | Dynamic morphogenesis of a pioneer axon in Drosophila and its regulation by Abl tyrosine kinase |
title_sort | dynamic morphogenesis of a pioneer axon in drosophila and its regulation by abl tyrosine kinase |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185889/ https://www.ncbi.nlm.nih.gov/pubmed/31967935 http://dx.doi.org/10.1091/mbc.E19-10-0563 |
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