Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany; Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland
Andrea Schink
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Masanari Takamiya
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Cédric Gobet
Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland
Alice Parisi
Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland
Andrei Yu Kobitski
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany; Institute of Applied Physics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Jonas Mertes
Institute of Applied Physics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Nils Krone
Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Uwe Strähle
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Institute of Biological and Chemical Systems – Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany; Institute of Applied Physics, Karlsruhe Institute of Technology, Karlsruhe, Germany; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, United States; Institute of Nanotechnology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Ralf Mikut
Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland
Philipp Gut
Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland
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.
