PUBLICATION

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

Authors
Weger, M., Weger, B.D., Schink, A., Takamiya, M., Stegmaier, J., Gobet, C., Parisi, A., Kobitski, A.Y., Mertes, J., Krone, N., Strähle, U., Nienhaus, G.U., Mikut, R., Gachon, F., Gut, P., Dickmeis, T.
ID
ZDB-PUB-201002-146
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Dickmeis, Thomas, Gut, Philipp, Mikut, Ralf, Parisi, Alice, Schink, Andrea, Strähle, Uwe, Takamiya, Masanari, Weger, Benjamin, Weger, Meltem
Keywords
carbohydrate response element, cholesterol, developmental biology, epiboly, genetics, genomics, metabolism, microtubule, pregnenolone, zebrafish
Datasets
GEO:GSE144350, GEO:GSE144349, GEO:GSE134778
MeSH Terms
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/metabolism
  • Cholesterol/genetics
  • Cholesterol/metabolism*
  • Embryo, Nonmammalian
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental/genetics*
  • Gene Knockdown Techniques
  • Zebrafish/embryology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
32969791 Full text @ Elife
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping