作者
Phan Q Duy, Stefan C Weise, Claudia Marini, Xiao-Jun Li, Dan Liang, Peter J Dahl, Shaojie Ma, Ana Spajic, Weilai Dong, Jane Juusola, Emre Kiziltug, Adam J Kundishora, Sunil Koundal, Maysam Z Pedram, Lucia A Torres-Fernández, Kristian Händler, Elena De Domenico, Matthias Becker, Thomas Ulas, Stefan A Juranek, Elisa Cuevas, Le Thi Hao, Bettina Jux, Andre MM Sousa, Fuchen Liu, Suel-Kee Kim, Mingfeng Li, Yiying Yang, Yutaka Takeo, Alvaro Duque, Carol Nelson-Williams, Yonghyun Ha, Kartiga Selvaganesan, Stephanie M Robert, Amrita K Singh, Garrett Allington, Charuta G Furey, Andrew T Timberlake, Benjamin C Reeves, Hannah Smith, Ashley Dunbar, Tyrone DeSpenza Jr, June Goto, Arnaud Marlier, Andres Moreno-De-Luca, Xin Yu, William E Butler, Bob S Carter, Evelyn MR Lake, R Todd Constable, Pasko Rakic, Haifan Lin, Engin Deniz, Helene Benveniste, Nikhil S Malvankar, Juvianee I Estrada-Veras, Christopher A Walsh, Seth L Alper, Joachim L Schultze, Katrin Paeschke, Angelika Doetzlhofer, F Gregory Wulczyn, Sheng Chih Jin, Richard P Lifton, Nenad Sestan, Waldemar Kolanus, Kristopher T Kahle
发表日期
2022/4
期刊
Nature neuroscience
卷号
25
期号
4
页码范围
458-473
出版商
Nature Publishing Group US
简介
Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a …
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PQ Duy, SC Weise, C Marini, XJ Li, D Liang, PJ Dahl… - Nature neuroscience, 2022