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A tug of war between DCC and ROBO1 signaling during commissural axon guidance

Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A m...

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Autores principales: Dailey-Krempel, Brianna, Martin, Andrew L., Jo, Ha-Neul, Junge, Harald J., Chen, Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335249/
https://www.ncbi.nlm.nih.gov/pubmed/37149867
http://dx.doi.org/10.1016/j.celrep.2023.112455
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author Dailey-Krempel, Brianna
Martin, Andrew L.
Jo, Ha-Neul
Junge, Harald J.
Chen, Zhe
author_facet Dailey-Krempel, Brianna
Martin, Andrew L.
Jo, Ha-Neul
Junge, Harald J.
Chen, Zhe
author_sort Dailey-Krempel, Brianna
collection PubMed
description Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A molecular mechanism that is hypothesized to underlie this switch in axonal responses is the silencing of Netrin1/Deleted in Colorectal Carcinoma (DCC)-mediated attraction by the repulsive SLIT/ROBO1 signaling. Using in vivo approaches including CRISPR-Cas9-engineered mouse models of distinct Dcc splice isoforms, we show here that commissural axons maintain responsiveness to both Netrin and SLIT during midline crossing, although likely at quantitatively different levels. In addition, full-length DCC in collaboration with ROBO3 can antagonize ROBO1 repulsion in vivo. We propose that commissural axons integrate and balance the opposing DCC and Roundabout (ROBO) signaling to ensure proper guidance decisions during midline entry and exit.
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spelling pubmed-103352492023-07-11 A tug of war between DCC and ROBO1 signaling during commissural axon guidance Dailey-Krempel, Brianna Martin, Andrew L. Jo, Ha-Neul Junge, Harald J. Chen, Zhe Cell Rep Article Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A molecular mechanism that is hypothesized to underlie this switch in axonal responses is the silencing of Netrin1/Deleted in Colorectal Carcinoma (DCC)-mediated attraction by the repulsive SLIT/ROBO1 signaling. Using in vivo approaches including CRISPR-Cas9-engineered mouse models of distinct Dcc splice isoforms, we show here that commissural axons maintain responsiveness to both Netrin and SLIT during midline crossing, although likely at quantitatively different levels. In addition, full-length DCC in collaboration with ROBO3 can antagonize ROBO1 repulsion in vivo. We propose that commissural axons integrate and balance the opposing DCC and Roundabout (ROBO) signaling to ensure proper guidance decisions during midline entry and exit. 2023-05-30 2023-05-05 /pmc/articles/PMC10335249/ /pubmed/37149867 http://dx.doi.org/10.1016/j.celrep.2023.112455 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Dailey-Krempel, Brianna
Martin, Andrew L.
Jo, Ha-Neul
Junge, Harald J.
Chen, Zhe
A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title_full A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title_fullStr A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title_full_unstemmed A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title_short A tug of war between DCC and ROBO1 signaling during commissural axon guidance
title_sort tug of war between dcc and robo1 signaling during commissural axon guidance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335249/
https://www.ncbi.nlm.nih.gov/pubmed/37149867
http://dx.doi.org/10.1016/j.celrep.2023.112455
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