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Krontira, A.C.* ; Cruceanu, C.* ; Dony, L. ; Kyrousi, C.* ; Link, M.H.* ; Rek, N.* ; Pöhlchen, D.* ; Raimundo, C.* ; Penner-Goeke, S.* ; Schowe, A.* ; Czamara, D.* ; Lahti-Pulkkinen, M.* ; Sammallahti, S.* ; Wolford, E.* ; Heinonen, K.* ; Roeh, S.* ; Sportelli, V.* ; Wölfel, B.* ; Ködel, M.* ; Sauer, S.* ; Rex-Haffner, M.* ; Räikkönen, K.* ; Labeur, M.* ; Cappello, S.* ; Binder, E.B.*

Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression.

Neuron 112, 1426-1443.e11 (2024)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Itu Cohort ; Mendelian Randomization ; Zbtb16 ; Cerebral Organoids ; Developing Mouse Cortex ; Dexamethasone ; Glucocorticoids ; Gyrified Species ; Neurogenesis ; Progenitors; Outer Subventricular Zone; Gene-expression; Disorders; Stress; Differentiation; Quantification; Proliferation; Phenotypes; Diversity; Pregnancy
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 0896-6273
e-ISSN 1097-4199
Journal Neuron
Quellenangaben Volume: 112, Issue: 9, Pages: 1426-1443.e11 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
Grants NARSAD Distinguished Investigator award
Hope for Depression Research Foundation
Joachim Herz Foundation
DOI 10.1016/j.neuron.2024.02.005
WOS ID 001238818600001
Scopus ID 85188464166
PubMed ID 38442714
Erfassungsdatum 2024-05-03
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