ZFIN ID: ZDB-PUB-201002-146
MondoA regulates gene expression in cholesterol biosynthesis-associated pathways required for zebrafish epiboly
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.
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
Microarrays: GEO:GSE134778, GEO:GSE144349, GEO:GSE144350
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
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.