Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00119264" target="_blank" >RIV/00216224:14310/21:00119264 - isvavai.cz</a>
Alternative codes found
RIV/67985904:_____/21:00548779 RIV/00216208:11110/21:10433256 RIV/00216208:11310/21:10433256 RIV/00216305:26620/21:PU141854
Result on the web
<a href="https://doi.org/10.1002/jbmr.4427" target="_blank" >https://doi.org/10.1002/jbmr.4427</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/jbmr.4427" target="_blank" >10.1002/jbmr.4427</a>
Alternative languages
Result language
angličtina
Original language name
Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling
Original language description
The Sprouty family is a highly conserved group of intracellular modulators of receptor tyrosine kinase (RTK)-signaling pathways, which have been recently linked to primary cilia. Disruptions in the structure and function of primary cilia cause inherited disorders called ciliopathies. We aimed to evaluate Sprouty2 and Sprouty4 gene-dependent alterations of ciliary structure and to focus on the determination of its association with Hedgehog signaling defects in chondrocytes. Analysis of the transgenic mice phenotype with Sprouty2 and Sprouty4 deficiency revealed several defects, including improper endochondral bone formation and digit patterning, or craniofacial and dental abnormalities. Moreover, reduced bone thickness and trabecular bone mass, skull deformities, or chondromalike lesions were revealed. All these pathologies might be attributed to ciliopathies. Elongation of the ciliary axonemes in embryonic and postnatal growth plate chondrocytes was observed in Sprouty2(-/-) and Sprouty2(+/-)/Sprouty4(-/-) mutants compared with corre- sponding littermate controls. Also, cilia-dependent Hedgehog signaling was upregulated in Sprouty2/4 mutant animals. Ptch1 and Ihh expression were upregulated in the autopodium and the proximal tibia of Sprouty2(-/-)/Sprouty4(-/-) mutants. Increased levels of the GLI3 repressor (GLI3R) form were detected in Sprouty2/4 mutant primary fibroblast embryonic cell cultures and tissues. These findings demonstrate that mouse lines deficient in Sprouty proteins manifest phenotypic features resembling ciliopathic phenotypes in multiple aspects and may serve as valuable models to study the association between overactivation of RTK and dysfunction of primary cilia during skeletogenesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10605 - Developmental biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Bone and Mineral Research
ISSN
0884-0431
e-ISSN
1523-4681
Volume of the periodical
36
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
2258-2274
UT code for WoS article
000697316300001
EID of the result in the Scopus database
2-s2.0-85115147593