DCDC2 Mutations Cause a Renal-Hepatic Ciliopathy by Disrupting Wnt Signaling
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F15%3A10294716" target="_blank" >RIV/00216208:11110/15:10294716 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/15:10294716
Result on the web
<a href="http://dx.doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" >http://dx.doi.org/10.1016/j.ajhg.2014.12.002</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" >10.1016/j.ajhg.2014.12.002</a>
Alternative languages
Result language
angličtina
Original language name
DCDC2 Mutations Cause a Renal-Hepatic Ciliopathy by Disrupting Wnt Signaling
Original language description
Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits beta-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Human Genetics
ISSN
0002-9297
e-ISSN
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Volume of the periodical
96
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
81-92
UT code for WoS article
000347707800006
EID of the result in the Scopus database
2-s2.0-84920729054