PUBLICATION

Involvement of nr2f genes in brain regionalization and eye development during early zebrafish development

Authors
Chowdhury, G., Umeda, K., Ohyanagi, T., Nasu, K., Yamasu, K.
ID
ZDB-PUB-240124-11
Date
2024
Source
Development, growth & differentiation   66(2): 145-160 (Journal)
Registered Authors
Yamasu, Kyo
Keywords
Nr2f/COUP-TF, brain development, eye, telencephalon, zebrafish
MeSH Terms
  • Animals
  • Brain/metabolism
  • Eye/metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Telencephalon/metabolism
  • Zebrafish*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
38263801 Full text @ Dev. Growth Diff.
Abstract
Nuclear receptor subfamily 2 group F (Nr2f) proteins are essential for brain development in mice, but little is known about their precise roles and their evolutionary diversification. In the present study, the expression patterns of major nr2f genes (nr2f1a, nr2f1b, and nr2f2) during early brain development were investigated in zebrafish. Comparisons of their expression patterns revealed similar but temporally and spatially distinct patterns after early somite stages in the brain. Frameshift mutations in the three nr2f genes, achieved using the CRISPR/Cas9 method, resulted in a smaller telencephalon and smaller eyes in the nr2f1a mutants; milder forms of those defects were present in the nr2f1b and nr2f2 mutants. Acridine orange staining revealed enhanced cell death in the brain and/or eyes in all nr2f homozygous mutants. The expression of regional markers in the brain did not suggest global defects in brain regionalization; however, shha expression in the preoptic area and hypothalamus, as well as fgf8a expression in the anterior telencephalon, was disturbed in nr2f1a and nr2f1b mutants, potentially leading to a defective telencephalon. Specification of the retina and optic stalk was also significantly affected. The overexpression of nr2f1b by injection of mRNA disrupted the anterior brain at a high dose, and the expression of pax6a in the eyes and fgf8a in the telencephalon at a low dose. The results of these loss- and gain-of-function approaches showed that nr2f genes regulate the development of the telencephalon and eyes in zebrafish embryos.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping