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| Status |
Public on Nov 29, 2023 |
| Title |
Cohesin composition and dosage independently affect early development in zebrafish |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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. Using zebrafish rad21 or stag2 mutants to change cohesin complex quantity or composition, we show that these parameters independently influence embryonic tailbud development. Both mutants have altered mesoderm induction, but only homozygous or heterozygous rad21 mutation affects cell cycle gene expression. stag2 mutants have slimmer notochords and reduced Wnt signaling in neuromesodermal progenitors as revealed by single cell RNA-sequencing. Stimulation of Wnt signaling rescues transcription and morphology in stag2, but not rad21 mutants, implying that individual cohesin mutations respond independently to cell signaling. Our results have implications for the understanding and management of cohesinopathies.
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| Overall design |
Tailbuds obtained from wild type and stag2b(nz207) were manually dissected and then dissociated using collagenase P and trypsin. Libraries were constructed using a 10X chromium platofrm according to standard 10X Genomics protocols. Libraries used 10X Chromium chemistry v2.
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| Contributor(s) |
Tatarakis D, Meier M, Schilling TF, Horsfield JA, Martin BL |
| Citation(s) |
38975838 |
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| Submission date |
Nov 29, 2023 |
| Last update date |
Sep 11, 2024 |
| Contact name |
Michael Meier |
| E-mail(s) |
michael.meier@otago.ac.nz
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| Phone |
0223177505
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| Organization name |
University of Otago
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| Department |
Pathology
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| Lab |
Chromosome structure and development group
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| Street address |
56 Hanover St
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| City |
Dunedin |
| State/province |
Region |
| ZIP/Postal code |
9016 |
| Country |
New Zealand |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1046494 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248952_RAW.tar |
551.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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