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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...

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Autores principales: Clarke, Akanni, McQueen, Philip G., Fang, Hsiao Yu, Kannan, Ramakrishnan, Wang, Victor, McCreedy, Evan, Buckley, Tyler, Johannessen, Erika, Wincovitch, Stephen, Giniger, Edward
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
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.
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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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