Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner

Luis Zurkirchen, Sandra Varum, Sonja Giger, Annika Klug, Jessica Häusel, Raphaël Bossart, Martina Zemke, Claudio Cantù, Zeynep Kalender Atak, Nicola Zamboni, Konrad Basler and Lukas Sommer ()
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Luis Zurkirchen: Institute of Anatomy, University of Zurich
Sandra Varum: Institute of Anatomy, University of Zurich
Sonja Giger: Institute of Anatomy, University of Zurich
Annika Klug: Institute of Anatomy, University of Zurich
Jessica Häusel: Institute of Anatomy, University of Zurich
Raphaël Bossart: Institute of Anatomy, University of Zurich
Martina Zemke: Institute of Anatomy, University of Zurich
Claudio Cantù: University of Zurich
Zeynep Kalender Atak: Laboratory of Computational Biology, KU Leuven Center for Human Genetics
Nicola Zamboni: Institute of Molecular Systems Biology, ETH Zurich
Konrad Basler: University of Zurich
Lukas Sommer: Institute of Anatomy, University of Zurich

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The transcription factor Yin Yang 1 (YY1) plays an important role in human disease. It is often overexpressed in cancers and mutations can lead to a congenital haploinsufficiency syndrome characterized by craniofacial dysmorphisms and neurological dysfunctions, consistent with a role in brain development. Here, we show that Yy1 controls murine cerebral cortex development in a stage-dependent manner. By regulating a wide range of metabolic pathways and protein translation, Yy1 maintains proliferation and survival of neural progenitor cells (NPCs) at early stages of brain development. Despite its constitutive expression, however, the dependence on Yy1 declines over the course of corticogenesis. This is associated with decreasing importance of processes controlled by Yy1 during development, as reflected by diminished protein synthesis rates at later developmental stages. Thus, our study unravels a novel role for Yy1 as a stage-dependent regulator of brain development and shows that biosynthetic demands of NPCs dynamically change throughout development.

Date: 2019
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DOI: 10.1038/s41467-019-09823-5

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