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MondoA regulates gene expression in cholesterol biosynthesis-associated pathways required for zebrafish epiboly

Weger, Meltem; Weger, Benjamin D; Schink, Andrea; Takamiya, Masanari; Stegmaier, Johannes; Gobet, Cédric; Parisi, Alice; Kobitski, Andrei Yu; Mertes, Jonas; Krone, Nils; Strähle, Uwe; Nienhaus, Gerd Ulrich; Mikut, Ralf; Gachon, Frédéric; Gut, Philipp; Dickmeis, Thomas

Abstract:
The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of mondoa impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects. Expression of genes in the terpenoid backbone and sterol biosynthesis pathways upstream of pregnenolone synthesis was coordinately downregulated in these embryos, including the most downregulated gene nsdhl. Loss of Nsdhl function likewise impaired epiboly, similar to MondoA loss of function. Both epiboly and microtubule defects were partially restored by pregnenolone treatment. Maternal-zygotic mutants of mondoa showed perturbed epiboly with low penetrance and compensatory changes in the expression of terpenoid/sterol/steroid metabolism genes. Collectively, our results show a novel role for MondoA in the regulation of early vertebrate development, connecting glucose, cholesterol and steroid hormone metabolism with early embryonic cell movements.

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Verlagsausgabe §
DOI: 10.5445/IR/1000125997
Veröffentlicht am 11.11.2020
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Physik (APH)
Institut für Automation und angewandte Informatik (IAI)
Institut für Nanotechnologie (INT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2050-084X
KITopen-ID: 1000125997
Erschienen in eLife
Band 9
Seiten Art. Nr. e57068
Vorab online veröffentlicht am 24.09.2020
Nachgewiesen in Scopus
Web of Science
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