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In vitro and in vivo models have successfully recapitulated multiple facets of the disorder, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic mechanisms underlying FAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we utilized an in vitro human pluripotent stem cell\u2010based (hPSC) model of corticogenesis to probe the effects of early, chronic intermittent alcohol exposure on the transcriptome of first trimester\u2010equivalent cortical neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We used RNA sequencing of developing hPSC\u2010derived neurons treated for 50\u00a0days with 50\u00a0mM ethanol and identified a relatively small number of biological pathways significantly altered by alcohol exposure. These included cell\u2010type specification, axon guidance, synaptic function, and regional patterning, with a notable upregulation of WNT signaling\u2010associated transcripts observed in alcohol\u2010exposed cultures relative to alcohol\u2010na\u00efve controls. Importantly, this effect paralleled a shift in gene expression of transcripts associated with regional patterning, such that caudal forebrain\u2010related transcripts were upregulated at the expense of more anterior ones. Results from H9 embryonic stem cells were largely replicated in an induced pluripotent stem cell line (IMR90\u20104), indicating that these patterning alterations are not cell line\u2010specific.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that a major effect of chronic intermittent alcohol on the developing cerebral cortex is an overall imbalance in regionalization, with enrichment of gene expression related to the production of posterodorsal progenitors and a diminution of anteroventral progenitors. This finding parallels behavioral and morphological phenotypes observed in animal models of high\u2010dose prenatal alcohol exposure, as well as patients with FAS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.14590","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T03:21:53Z","timestamp":1615173713000},"page":"979-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Transcriptomic changes due to early, chronic intermittent alcohol exposure during forebrain development implicate WNT signaling, cell\u2010type specification, and cortical regionalization as primary determinants of fetal alcohol syndrome"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-5039","authenticated-orcid":false,"given":"M\u00e1t\u00e9","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Neurosciences University of New Mexico 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