PUBLICATION

Slit2 is necessary for optic axon organization in the zebrafish ventral midline

Authors
Davison, C., Zolessi, F.R.
ID
ZDB-PUB-210519-6
Date
2021
Source
Cells & development   166: 203677 (Journal)
Registered Authors
Zolessi, Flavio
Keywords
Axon guidance, CRISPR-Cas9, Optic chiasm, Optic nerve, Optic tract, Retinotopic order
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Axons/metabolism*
  • Base Sequence
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Intracellular Signaling Peptides and Proteins/chemistry
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Models, Biological
  • Mutation/genetics
  • Optic Chiasm/metabolism*
  • Optic Nerve/metabolism*
  • Retinal Ganglion Cells/metabolism
  • Visual Pathways
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33994352 Full text @ Cells Dev
Abstract
Slit-Robo signaling has been implicated in regulating several steps of retinal ganglion cell axon guidance, with a central role assigned to Slit2. We report here the phenotypical characterization of a CRISPR-Cas9-generated zebrafish null mutant for this gene, along with a detailed analysis of its expression pattern by WM-FISH. All evident defects in the optic axons in slit2-/- mutants were detected outside the retina, coincident with the major sites of expression at the ventral forebrain, around the developing optic nerve and anterior to the optic chiasm/proximal tract. Anterograde axon tracing experiments in zygotic and maternal-zygotic mutants, as well as morphants, showed the occurrence of axon sorting defects, which appeared mild at the optic nerve level, but more severe in the optic chiasm and the proximal tract. A remarkable sorting defect was the usual splitting of one of the optic nerves in two branches that surrounded the contralateral nerve at the chiasm. Although all axons eventually crossed the midline, the retinotopic order appeared lost at the proximal optic tract, to eventually correct distally. Time-lapse analysis demonstrated the sporadic occurrence of axon misrouting at the chiasm level, which could be responsible for the sorting errors. Our results support previous evidence of a channeling role for Slit molecules in retinal ganglion cell axons at the optic nerve, in addition to a function in the segregation of axons coming from each nerve and from different retinal regions at the medio-ventral area of the forebrain.
Errata / Notes
Correction: https://www.sciencedirect.com/science/article/pii/S2667290121000838?via%3Dihub Corrects: https://www.sciencedirect.com/science/article/pii/S2667290121000243
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping