{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tomita H"],"funding":["NICHD NIH HHS","NCATS NIH HHS","NIEHS NIH HHS","National Institutes of Health","NIH HHS","NIGMS NIH HHS","Smith-Lemli-Opitz/RSH Foundation"],"pagination":["e67141"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9519149"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11"],"pubmed_abstract":["Defective 3β-hydroxysterol-Δ<sup>7</sup> -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of <i>DHCR7</i> causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of <i>DHCR7</i> or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/E"],"journal":["eLife"],"pubmed_title":["7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome."],"pmcid":["PMC9519149"],"funding_grant_id":["T32 GM007750","P30 ES007033","R01 HD092659","Research grant","TL1 TR002318","T32 ES007032"],"pubmed_authors":["Xu L","Herron JM","Baggett DW","Tomita H","Li A","Hines KM"],"additional_accession":[]},"is_claimable":false,"name":"7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome.","description":"Defective 3β-hydroxysterol-Δ<sup>7</sup> -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of <i>DHCR7</i> causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of <i>DHCR7</i> or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/E","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-05-28T00:34:53.757Z","creation":"2025-04-19T05:16:00.334Z"},"accession":"S-EPMC9519149","cross_references":{"pubmed":["36111785"],"doi":["10.7554/eLife.67141"]}}