PUBLICATION

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

Authors: Davison, C., Bedó, G., Zolessi, F.R.
ID: ZDB-PUB-221025-16
Date: 2022
Source: Journal of developmental biology 10(4): (Journal)
Registered Authors: Davison, Camilia, Zolessi, Flavio
Keywords: CRISPR-Cas9, axon guidance, optic chiasm, optic nerve, optic tract, retinal ganglion cells, tectum
MeSH Terms: none
PubMed: 36278546 Full text @ J Dev Biol

Abstract

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 slit3 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 slit3 expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the slit2 mutant, while the same treatment in the slit2-/-^mz background caused much more severe defects, comparable to those observed in robo2 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 slit2 expression in slit3-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.

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