Cohesin composition and dosage independently affect early development in zebrafish.

Autor:	Labudina AA; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Meier M; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Gimenez G; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Tatarakis D; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697-2300, USA., Ketharnathan S; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Mackie B; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Schilling TF; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697-2300, USA., Antony J; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand., Horsfield JA; Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9016, New Zealand.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Aug 01; Vol. 151 (15). Date of Electronic Publication: 2024 Aug 01.
DOI:	10.1242/dev.202593
Abstrakt:	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 characterized by germline variants of cohesin or its regulators that do not entirely eliminate cohesin function. However, it is not clear whether 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. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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