GPMLS and BMC Seminar Monday, 2nd March in Reykjavik University at 15:00 room V-101
Speaker: Thomas Dickmeis, professor at the Institute of Toxicology and Genetics við Karlsruhe Institute of Technology, Germany
Title: Regulation of cholesterol biogenesis by the glucose-sensing transcription factor MondoA is required for zebrafish epiboly
Abstract: Mondo transcription factors mediate glucose-induced gene transcription and regulate energy metabolism in mammalian tissues. We demonstrate that the zebrafish Mondo pathway equally transduces glucose signaling, showing its conserved function within the vertebrates. Importantly, loss of zebrafish mondoa function severely impairs epiboly, revealing an important role for Mondo signaling in development. Computational analysis of digital scanned laser light sheet microscopy data reveals that the disruption is specific to epiboly, while internalization of cells at the margin occurs with normal migration speed. Furthermore, total cell numbers are highly similar to control embryos, excluding cell proliferation defects as a cause for impaired epiboly. Transcriptome analysis identified Nsdhl, a key enzyme in the cholesterol synthesis pathway, as a main downstream target of MondoA. Consistently, loss of nsdhl function equally impairs epiboly. Cholesterol serves as substrate for the first step of steroid hormone biosynthesis, pregnenolone formation. Remarkably, pregnenolone treatment of mondoa morphants rescues microtubule cytoskeleton defects and partially restores epiboly, indicating a crucial function for this hormone downstream of MondoA. Our results link MondoA function to cholesterol and steroid hormone synthesis and reveal a novel role in vertebrate embryonic development for MondoA regulated transcription.
Biography: Thomas Dickmeis was born in Aachen, Germany, in 1971. After studying biology in Aachen, Freiburg (Germany) and Madrid (Spain), he graduated at the University of Freiburg in 1999. He then pursued doctoral studies in the laboratory of Uwe Strähle at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg, France. In 2002 he received his PhD from the Université Louis Pasteur for his work on target genes of the Nodal signalling pathway in the early zebrafish embryo. After a postdoctoral stay in the laboratory of Nicholas Foulkes at the Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany, where he examined connections between the circadian clock, cell proliferation and glucocorticoid signalling in zebrafish larvae, he was appointed research group leader at the Institute of Toxicology and Genetics (ITG) within the Karlsruhe Institute of Technology (KIT) in Karlsruhe, Germany, in 2008. His current research interests are centered on zebrafish endocrinology and metabolism.