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Cohesin composition and dosage independently affect early development in zebrafish
Anastasia A Labudina1, Michael Meier1, Gregory Gimenez1
1Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand.
Development (Cambridge, England)
|July 8, 2024
Summary
Mutations in cohesin subunits Rad21 and Stag2b independently affect zebrafish development, influencing mesoderm induction and Wnt signaling. This highlights distinct consequences of cohesin quantity versus composition changes in cohesinopathies.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Cohesin is a crucial protein complex regulating gene expression and cell proliferation in metazoans.
- Cohesinopathies are human developmental disorders linked to cohesin or its regulators, but the impact of individual subunit mutations remains unclear.
Purpose of the Study:
- To investigate the independent developmental consequences of mutations in individual cohesin subunits, specifically rad21 and stag2b, in zebrafish.
- To elucidate the distinct molecular mechanisms underlying these developmental effects.
Main Methods:
- Zebrafish mutagenesis (rad21 and stag2b mutants).
- Analysis of embryonic tailbud development, mesoderm induction, and cell cycle gene expression.
- Single-cell RNA sequencing to assess Wnt signaling in neuromesodermal progenitors.
- Wnt signaling pathway stimulation to test rescue effects.
Main Results:
- Both rad21 and stag2b mutants exhibited altered mesoderm induction.
- rad21 mutants (homozygous/heterozygous) showed affected cell cycle gene expression.
- stag2b mutants displayed narrower notochords and reduced Wnt signaling in neuromesodermal progenitors.
- Wnt signaling stimulation rescued transcription and morphology in stag2b mutants, but not in rad21 mutants.
Conclusions:
- Mutations affecting cohesin quantity versus composition have independent developmental consequences.
- Distinct roles of rad21 and stag2b in zebrafish embryonic development are identified.
- Findings provide insights into the pathogenesis of cohesinopathies and potential therapeutic strategies.
