Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline

Slit-Robo signaling regulates midline crossing of commissural axons in different systems. In zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely repr...

Full description

Bibliographic Details
Main Authors: Camila Davison, Gabriela Bedó, Flavio R. Zolessi
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Journal of Developmental Biology
Subjects:
Online Access:https://www.mdpi.com/2221-3759/10/4/41
_version_ 1827638414876344320
author Camila Davison
Gabriela Bedó
Flavio R. Zolessi
author_facet Camila Davison
Gabriela Bedó
Flavio R. Zolessi
author_sort Camila Davison
collection DOAJ
description Slit-Robo signaling regulates midline crossing of commissural axons in different systems. In zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely reproduced in a Slit2 ligand null mutant. Since <i>slit3</i> is also expressed around this area at the stage of axon crossing, we decided to analyze the possibility that it collaborates with Slit2 in this process. We found that the disruption of <i>slit3</i> expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the <i>slit2</i> mutant, while the same treatment in the <i>slit2−/−<sup>mz</sup></i> background caused much more severe defects, comparable to those observed in <i>robo2</i> mutants. Tracking analysis of in vivo time-lapse experiments indicated differential but complementary functions of these secreted factors in the correction of axon turn errors around the optic chiasm. Interestingly, RT-qPCR analysis showed a mild increase in <i>slit2</i> expression in <i>slit3</i>-deficient embryos, but not the opposite. Our observations support the previously proposed “repulsive channel” model for Slit-Robo action at the optic chiasm, with both Slits acting in different manners, most probably relating to their different spatial expression patterns.
first_indexed 2024-03-09T16:16:05Z
format Article
id doaj.art-aa701e3eb7254ce8af11eeab4478ad67
institution Directory Open Access Journal
issn 2221-3759
language English
last_indexed 2024-03-09T16:16:05Z
publishDate 2022-09-01
publisher MDPI AG
record_format Article
series Journal of Developmental Biology
spelling doaj.art-aa701e3eb7254ce8af11eeab4478ad672023-11-24T15:48:23ZengMDPI AGJournal of Developmental Biology2221-37592022-09-011044110.3390/jdb10040041Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the MidlineCamila Davison0Gabriela Bedó1Flavio R. Zolessi2Sección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguaySección Genética Evolutiva, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguaySección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguaySlit-Robo signaling regulates midline crossing of commissural axons in different systems. In zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely reproduced in a Slit2 ligand null mutant. Since <i>slit3</i> is also expressed around this area at the stage of axon crossing, we decided to analyze the possibility that it collaborates with Slit2 in this process. We found that the disruption of <i>slit3</i> expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the <i>slit2</i> mutant, while the same treatment in the <i>slit2−/−<sup>mz</sup></i> background caused much more severe defects, comparable to those observed in <i>robo2</i> mutants. Tracking analysis of in vivo time-lapse experiments indicated differential but complementary functions of these secreted factors in the correction of axon turn errors around the optic chiasm. Interestingly, RT-qPCR analysis showed a mild increase in <i>slit2</i> expression in <i>slit3</i>-deficient embryos, but not the opposite. Our observations support the previously proposed “repulsive channel” model for Slit-Robo action at the optic chiasm, with both Slits acting in different manners, most probably relating to their different spatial expression patterns.https://www.mdpi.com/2221-3759/10/4/41optic chiasmaxon guidanceretinal ganglion cellsoptic nerveoptic tracttectum
spellingShingle Camila Davison
Gabriela Bedó
Flavio R. Zolessi
Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
Journal of Developmental Biology
optic chiasm
axon guidance
retinal ganglion cells
optic nerve
optic tract
tectum
title Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
title_full Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
title_fullStr Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
title_full_unstemmed Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
title_short Zebrafish Slit2 and Slit3 Act Together to Regulate Retinal Axon Crossing at the Midline
title_sort zebrafish slit2 and slit3 act together to regulate retinal axon crossing at the midline
topic optic chiasm
axon guidance
retinal ganglion cells
optic nerve
optic tract
tectum
url https://www.mdpi.com/2221-3759/10/4/41
work_keys_str_mv AT camiladavison zebrafishslit2andslit3acttogethertoregulateretinalaxoncrossingatthemidline
AT gabrielabedo zebrafishslit2andslit3acttogethertoregulateretinalaxoncrossingatthemidline
AT flaviorzolessi zebrafishslit2andslit3acttogethertoregulateretinalaxoncrossingatthemidline