{"id":23517,"date":"2019-07-30T00:00:10","date_gmt":"2019-07-30T07:00:10","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=23517"},"modified":"2024-01-30T14:53:08","modified_gmt":"2024-01-30T22:53:08","slug":"finding-a-cause-of-neurodevelopmental-disorders","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/finding-a-cause-of-neurodevelopmental-disorders\/","title":{"rendered":"Finding a cause of neurodevelopmental disorders"},"content":{"rendered":"<p>LA JOLLA\u2014Neurodevelopmental disorders arising from rare genetic mutations can cause atypical cognitive function, intellectual disability, and developmental delays, yet it is unclear why and how this happens.\u00a0Scientists suspected a mutation in a complex of proteins could be the culprit for a group of rare genetic disorders and, now, Salk Institute researchers have identified the molecular mechanism linking this mutation with abnormal nervous system development. The team\u2019s findings, published in <a href=\"https:\/\/www.cell.com\/molecular-cell\/fulltext\/S1097-2765(19)30480-0\" target=\"_blank\" rel=\"noopener\"><em>Molecular Cell<\/em><\/a> on July 30, 2019, bring researchers one step closer to understanding neurodevelopmental disorders, such as Nicolaides-Baraitser syndrome and others.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-VzntY6N-9XI\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/VzntY6N-9XI?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>\u201cFor the first time, we have been able to characterize the mechanism of a known gene mutation implicated in neurodevelopmental disorders,\u201d says Assistant Professor <a href=\"https:\/\/www.salk.edu\/zh\/scientist\/diana-hargreaves\/\">Diana Hargreaves<\/a>, senior author and holder of the Richard Heyman and Anne Daigle Endowed Developmental Chair.<\/p>\n<figure id=\"attachment_23582\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"300\" class=\"image-responsive wp-image-23582 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-300x300.jpg\" alt=\"Neurons generated using the cell culture method described in the paper. \" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-300x300.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-150x150.jpg 150w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-768x768.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-767x767.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-147x147.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-458x458.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-585x585.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-553x553.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-750x750.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-945x945.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-400x400.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves-200x200.jpg 200w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves.jpg 1024w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><figcaption class=\"wp-caption-text\">Neurons generated using the cell culture method described in the paper. <\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/ScienceImage-hargreaves.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>Credit: Salk Institute<\/figcaption><\/figure>\n<p>The root cause has to do with a complex of proteins called the SWI\/SNF complex, which is involved in DNA regulation, and, when mutated, is associated with Nicolaides-Baraitser syndrome, Coffin-Siris syndrome, autism and even some cancers. These complexes repackage and reshape the DNA in the nucleus to either enable or prevent access to genes. And yet, scientists do not know how mutations in individual subunits of the SWI\/SNF complex affect its function.<\/p>\n<p>\u201cWe sought to understand how a single mutation in the SMARCA2 subunit affected brain development,\u201d says Fangjian Gao, the paper\u2019s first author and a postdoctoral fellow at Salk. \u201cWe expected to see some effect on the neurodevelopmental pathways, but we were not sure how, specifically.\u201d<\/p>\n<figure id=\"attachment_23521\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"200\" class=\"img-responsive wp-image-23521 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-300x200.jpg\" alt=\"From left: Diana Hargreaves, Nicholas Elliott and Fangjian Gao.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-767x511.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-945x630.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-1250x833.jpg 1250w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl-400x267.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl.jpg 1500w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">From left: Diana Hargreaves, Nicholas Elliott and Fangjian Gao.<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2019\/07\/PR_Hargreaves_Gao_Elliott_551A1276_fnl.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>Credit: Salk Institute<\/figcaption><\/figure>\n<p>The scientists turned to cell cultures in a dish to model growth patterns in afflicted brain cells versus normal brain cells. They used the gene-editing technique CRISPR to mimic the SMARCA2 mutation observed in Nicolaides-Baraitser syndrome. Notably, the researchers found that healthy cells had minimal SMARCA2 activity. The cells with the mutation, however, had a dramatic increase in SMARCA2 activity and a significantly impaired ability to generate precursors to neurons, called neural progenitor cells. In this highly activated state, SMARCA2 affected the function of the normal SWI\/SNF complex. This led to a domino effect with changes in gene expression resulting in abnormal brain development.<\/p>\n<p>\u201cBy better understanding this mutation in SMARCA2, we have tapped into what looks like a core developmental process that could be perturbed in disease states such as autism or even cancer,\u201d says Hargreaves.<\/p>\n<p>Other authors included Nicholas J. Elliott, Josephine Ho and Maxim N. Shokhirev of Salk, along with Alexzander Sharp of the University of California San Diego.<\/p>\n<p>The work was funded by the Helmsley Trust, the National Institutes of Health (9R35 GM128943-01 and R00 CA184043-03) and the V Foundation for Cancer Research (V2016-006).<\/p>","protected":false},"featured_media":23582,"template":"","faculty":[74],"disease-research":[124],"class_list":["post-23517","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-diana-hargreaves","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Finding a cause of neurodevelopmental disorders - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/finding-a-cause-of-neurodevelopmental-disorders\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Finding a cause of neurodevelopmental disorders - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Neurodevelopmental disorders arising from rare genetic mutations can cause atypical cognitive function, intellectual disability, and developmental delays, yet it is unclear why and how this happens.\u00a0Scientists suspected a mutation in a complex of proteins could be the culprit for a group of rare genetic disorders and, now, Salk Institute researchers have identified the molecular mechanism linking this mutation with abnormal nervous system development. 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