Human neurogenesis is altered via glucocorticoid-mediated regulation of<i>ZBTB16</i>expression
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 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 drive cortical expansion in gyrified species. This effect is mediated via the transcription factorZBTB16and leads to increased production of neurons. A phenome-wide mendelian randomization analysis of an enhancer variant that moderates glucocorticoid-inducedZBTB16levels, reveals causal relationships with higher educational attainment and altered brain structure. The relationship with postnatal cognition is supported by data from a prospective pregnancy cohort. This study provides a novel cellular and molecular pathway for the effects of glucocorticoids on human neurogenesis that relates to lasting postnatal phenotypes..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 12. Juli Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Krontira, Anthi C. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.08.21.504700 |
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| PPN (Katalog-ID): |
XBI036978965 |
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| 520 | |a 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 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 drive cortical expansion in gyrified species. This effect is mediated via the transcription factorZBTB16and leads to increased production of neurons. A phenome-wide mendelian randomization analysis of an enhancer variant that moderates glucocorticoid-inducedZBTB16levels, reveals causal relationships with higher educational attainment and altered brain structure. The relationship with postnatal cognition is supported by data from a prospective pregnancy cohort. This study provides a novel cellular and molecular pathway for the effects of glucocorticoids on human neurogenesis that relates to lasting postnatal phenotypes. | ||
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| 700 | 1 | |a Binder, Elisabeth B. |4 aut | |
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