PUBLICATION
Cohesin composition and dosage independently affect early development in zebrafish
- Authors
- Labudina, A.A., Meier, M., Gimenez, G., Tatarakis, D., Ketharnathan, S., Mackie, B., Schilling, T.F., Antony, J., Horsfield, J.A.
- ID
- ZDB-PUB-240709-6
- Date
- 2024
- Source
- Development (Cambridge, England) 151(15): (Journal)
- Registered Authors
- Antony, Jisha, Horsfield, Jules, Labudina, Anastasia, Meier, Michael, Schilling, Tom
- Keywords
- Cell fate, Cohesin, Rad21, Stag2, Zebrafish
- Datasets
- GEO:GSE247246, GEO:GSE248952
- MeSH Terms
-
- Animals
- Cell Cycle Proteins*/genetics
- Cell Cycle Proteins*/metabolism
- Chromosomal Proteins, Non-Histone*/genetics
- Chromosomal Proteins, Non-Histone*/metabolism
- Cohesins*
- Embryonic Development/genetics
- Gene Dosage
- Gene Expression Regulation, Developmental
- Mesoderm/embryology
- Mesoderm/metabolism
- Mutation*/genetics
- Wnt Signaling Pathway/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38975838 Full text @ Development
Citation
Labudina, A.A., Meier, M., Gimenez, G., Tatarakis, D., Ketharnathan, S., Mackie, B., Schilling, T.F., Antony, J., Horsfield, J.A. (2024) Cohesin composition and dosage independently affect early development in zebrafish. Development (Cambridge, England). 151(15):.
Abstract
Cohesin, a chromatin-associated protein complex with four core subunits (Smc1a, Smc3, Rad21 and either Stag1 or 2), has a central role in cell proliferation and gene expression in metazoans. Human developmental disorders termed "cohesinopathies" are characterised by germline mutations in cohesin or its regulators that do not entirely eliminate cohesin function. However, it is not clear if mutations in individual cohesin subunits have independent developmental consequences. Here we show that zebrafish rad21 or stag2b mutants independently influence embryonic tailbud development. Both mutants have altered mesoderm induction, but only homozygous or heterozygous rad21 mutation affects cell cycle gene expression. stag2b mutants have narrower notochords and reduced Wnt signaling in neuromesodermal progenitors as revealed by single cell RNA-sequencing. Stimulation of Wnt signaling rescues transcription and morphology in stag2b, but not rad21 mutants. Our results suggest that mutations altering the quantity versus composition of cohesin have independent developmental consequences, with implications for the understanding and management of cohesinopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping