Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression.
Journal: Neuron
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Affiliated Institutions:
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany; International Max Planck Research School for Translational Psychiatry, Munich , Germany. Electronic address: anthi.krontira@bmc.med.lmu.de.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm , Sweden.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany; International Max Planck Research School for Translational Psychiatry, Munich , Germany; Department for Computational Health, Helmholtz Munich, Neuherberg , Germany; TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising , Germany.
Developmental Neurobiology, Max Planck Institute of Psychiatry, Munich , Germany; First Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, Eginition Hospital, Athens , Greece; University Mental Health, Neurosciences and Precision Medicine Research Institute "Costas Stefanis", Athens , Greece.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany; International Max Planck Research School for Translational Psychiatry, Munich , Germany.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany; Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University, Munich , Germany.
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki , Finland; Finnish Institute for Health and Welfare, Helsinki , Finland; Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH TJ, UK.
Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki , Finland.
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki , Finland.
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki , Finland; Psychology/Welfare, Faculty of Social Sciences, University of Tampere, Tampere , Finland; Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON MT P, Canada.
Developmental Neurobiology, Max Planck Institute of Psychiatry, Munich , Germany; Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-University (LMU), Munich , Germany.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich , Germany. Electronic address: binder@psych.mpg.de.
Abstract summary
Glucocorticoids are important for proper organ maturation, and their levels are tightly regulated during development. Here, we use human cerebral organoids and mice to study the cell-type-specific effects of glucocorticoids on neurogenesis. We show that glucocorticoids increase a specific type of basal progenitors (co-expressing PAX6 and EOMES) that has been shown to contribute to cortical expansion in gyrified species. This effect is mediated via the transcription factor ZBTB16 and leads to increased production of neurons. A phenome-wide Mendelian randomization analysis of an enhancer variant that moderates glucocorticoid-induced ZBTB16 levels reveals causal relationships with higher educational attainment and altered brain structure. The relationship with postnatal cognition is also supported by data from a prospective pregnancy cohort study. This work provides a cellular and molecular pathway for the effects of glucocorticoids on human neurogenesis that relates to lasting postnatal phenotypes.
Authors & Co-authors:
Krontira
Cruceanu
Dony
Kyrousi
Link
Rek
Pöhlchen
Raimundo
Penner-Goeke
Schowe
Czamara
Lahti-Pulkkinen
Sammallahti
Wolford
Heinonen
Roeh
Sportelli
Wölfel
Ködel
Sauer
Rex-Haffner
Räikkönen
Labeur
Cappello
Binder
Study Outcome
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