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@ARTICLE{Duy:163752,
author = {Duy, Phan Q and Weise, Stefan C and Marini, Claudia and Li,
Xiao-Jun and Liang, Dan and Dahl, Peter J and Ma, Shaojie
and Spajic, Ana and Dong, Weilai and Juusola, Jane and
Kiziltug, Emre and Kundishora, Adam J and Koundal, Sunil and
Pedram, Maysam Z and Torres-Fernández, Lucia A and
Händler, Kristian and de Domenico, Elena and Becker,
Matthias Kai Holger and Ulas, Thomas and Juranek, Stefan A
and Cuevas, Elisa and Hao, Le Thi and Jux, Bettina and
Sousa, André M M and Liu, Fuchen and Kim, Suel-Kee and Li,
Mingfeng and Yang, Yiying and Takeo, Yutaka and Duque,
Alvaro and Nelson-Williams, Carol and Ha, Yonghyun and
Selvaganesan, Kartiga and Robert, Stephanie M and Singh,
Amrita K and Allington, Garrett and Furey, Charuta G and
Timberlake, Andrew T and Reeves, Benjamin C and Smith,
Hannah and Dunbar, Ashley and DeSpenza, Tyrone and Goto,
June and Marlier, Arnaud and Moreno-De-Luca, Andres and Yu,
Xin and Butler, William E and Carter, Bob S and Lake, Evelyn
M R and Constable, R Todd and Rakic, Pasko and Lin, Haifan
and Deniz, Engin and Benveniste, Helene and Malvankar,
Nikhil S and Estrada-Veras, Juvianee I and Walsh,
Christopher A and Alper, Seth L and Schultze, Joachim and
Paeschke, Katrin and Doetzlhofer, Angelika and Wulczyn, F
Gregory and Jin, Sheng Chih and Lifton, Richard P and
Sestan, Nenad and Kolanus, Waldemar and Kahle, Kristopher T},
title = {{I}mpaired neurogenesis alters brain biomechanics in a
neuroprogenitor-based genetic subtype of congenital
hydrocephalus.},
journal = {Nature neuroscience},
volume = {25},
number = {4},
issn = {1097-6256},
address = {New York, NY},
publisher = {Nature America},
reportid = {DZNE-2022-00491},
pages = {458 - 473},
year = {2022},
abstract = {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
hypercompliant cortex and secondary ventricular enlargement
without primary defects in CSF circulation. These data
highlight the importance of precisely regulated
neuroepithelial cell fate for normal brain-CSF biomechanics
and support a clinically relevant neuroprogenitor-based
paradigm of CH.},
keywords = {Exome Sequencing / Animals / Biomechanical Phenomena /
Brain: metabolism / Cerebrospinal Fluid: metabolism / Humans
/ Hydrocephalus: cerebrospinal fluid / Hydrocephalus:
genetics / Mice / Neurogenesis: genetics / Tripartite Motif
Proteins: genetics / Tripartite Motif Proteins: metabolism /
Ubiquitin-Protein Ligases: genetics / Whole Exome Sequencing
/ Tripartite Motif Proteins (NLM Chemicals) / TRIM71
protein, human (NLM Chemicals) / Ubiquitin-Protein Ligases
(NLM Chemicals)},
cin = {AG Schultze / $R\&D$ PRECISE / Modular High Performance
Computing},
ddc = {610},
cid = {I:(DE-2719)1013031 / I:(DE-2719)5000031 /
I:(DE-2719)5000079},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9664907},
pubmed = {pmid:35379995},
doi = {10.1038/s41593-022-01043-3},
url = {https://pub.dzne.de/record/163752},
}