<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Krontira, Anthi C</style></author><author><style face="normal" font="default" size="100%">Cruceanu, Cristiana</style></author><author><style face="normal" font="default" size="100%">Kyrousi, Christina</style></author><author><style face="normal" font="default" size="100%">Dony, Leander</style></author><author><style face="normal" font="default" size="100%">Link, Marie-Helen</style></author><author><style face="normal" font="default" size="100%">Kappelmann, Nils</style></author><author><style face="normal" font="default" size="100%">Pöhlchen, Dorothee</style></author><author><style face="normal" font="default" size="100%">Roeh, Simone</style></author><author><style face="normal" font="default" size="100%">Sportelli, Vincenza</style></author><author><style face="normal" font="default" size="100%">Wölfel, Barbara</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Temporal regulation of ZBTB16 expression by glucocorticoids alters human cortical neurogenesis</style></title><secondary-title><style face="normal" font="default" size="100%">bioRxiv</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2022</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.biorxiv.org/content/10.1101/2022.08.21.504700v1</style></url></web-urls></urls><publisher><style face="normal" font="default" size="100%">Cold Spring Harbor Laboratory</style></publisher><pages><style face="normal" font="default" size="100%">2022.08. 21.504700</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Glucocorticoids are important for proper organ maturation&lt;sup&gt;&lt;a id=&quot;xref-ref-1-1&quot; class=&quot;xref-bibr&quot; href=&quot;https://www.biorxiv.org/content/10.1101/2022.08.21.504700v1#ref-1&quot;&gt;1&lt;/a&gt;&lt;/sup&gt;. Increased exposure to these hormones during pregnancy, as a result of commonly prescribed synthetic glucocorticoids such as dexamethasone in preterm births&lt;sup&gt;&lt;a id=&quot;xref-ref-2-1&quot; class=&quot;xref-bibr&quot; href=&quot;https://www.biorxiv.org/content/10.1101/2022.08.21.504700v1#ref-2&quot;&gt;2&lt;/a&gt;&lt;/sup&gt;, has been associated with lasting effects on the offspring, including on neurodevelopment and neuropsychiatric disease risk&lt;sup&gt;&lt;a id=&quot;xref-ref-3-1&quot; class=&quot;xref-bibr&quot; href=&quot;https://www.biorxiv.org/content/10.1101/2022.08.21.504700v1#ref-3&quot;&gt;3&lt;/a&gt;&lt;/sup&gt;. While the consequences of glucocorticoid excess in term and especially adult brain have been extensively studied, mainly in rodents&lt;sup&gt;&lt;a id=&quot;xref-ref-4-1&quot; class=&quot;xref-bibr&quot; href=&quot;https://www.biorxiv.org/content/10.1101/2022.08.21.504700v1#ref-4&quot;&gt;4&lt;/a&gt;&lt;/sup&gt;, studies on their effects during early human cortical development are absent. Here we use human cerebral organoids and mice to study cell-type specific effects of glucocorticoids on neurogenic processes. We show that glucocorticoid administration during neurogenesis alters the cellular architecture of the developing cortex by increasing a specific type of gyrencephalic species-enriched basal progenitors that co-express &lt;em&gt;PAX6&lt;/em&gt; and &lt;em&gt;EOMES&lt;/em&gt;. This effect is mediated via the glucocorticoid-responsive transcription factor &lt;em&gt;ZBTB16&lt;/em&gt; as shown with overexpression, genetic knock-down and reporter assays experiments in organoids and embryonic mouse models and leads to increased production of deep-layer neurons. A phenome-wide mendelian randomization analysis of a genetic intronic enhancer variant that moderates glucocorticoid-induced &lt;em&gt;ZBTB16&lt;/em&gt; levels, as shown with enhancer assays and enhancer-editing in organoids, reveals potential causal relationships with increased educational attainment as well as neuroimaging phenotypes in adults. In this study we provide a cellular and molecular pathway for the effects of glucocorticoids on human neurogenesis that potentially explains postnatal phenotypes and may be used to refine treatment guidelines.</style></abstract></record></records></xml>