Detail publikace

Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling

HRUBÁ, E. KAVKOVÁ, M. DALECKÁ, L. MACHOLÁN, M. ZIKMUND, T. VAŘECHA, M. BOSÁKOVÁ, M. KAISER, J. KREJČÍ, P. HOVOŘÁKOVÁ, M. BUCHTOVÁ, M.

Originální název

Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

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. (C) 2021 American Society for Bone and Mineral Research (ASBMR).

Klíčová slova

BONE QCT/mu CT; ANALYSIS/QUANTITATION OF BONE; GENETIC ANIMAL MODELS; MOLECULAR PATHWAYS - DEVELOPMENT; LIMB PATTERNING; BONE MODELING AND REMODELING; HEDGEHOG; CELL/TISSUE SIGNALING

Autoři

HRUBÁ, E.; KAVKOVÁ, M.; DALECKÁ, L.; MACHOLÁN, M.; ZIKMUND, T.; VAŘECHA, M.; BOSÁKOVÁ, M.; KAISER, J.; KREJČÍ, P.; HOVOŘÁKOVÁ, M.; BUCHTOVÁ, M.

Vydáno

25. 8. 2021

Nakladatel

WILEY

Místo

HOBOKEN

ISSN

0884-0431

Periodikum

JOURNAL OF BONE AND MINERAL RESEARCH

Ročník

15

Číslo

124

Stát

Spojené státy americké

Strany od

1

Strany do

17

Strany počet

17

URL

https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4427

BibTex

@article{BUT172867,
  author="Eva {Hrubá} and Michaela {Kavková} and Linda {Dalecká} and Miloš {Macholán} and Tomáš {Zikmund} and Miroslav {Vařecha} and Michaela {Bosáková} and Jozef {Kaiser} and Pavel {Krejčí} and Mária {Hovořáková} and Marcela {Buchtová}",
  title="Loss of Sprouty Produces a Ciliopathic Skeletal Phenotype in Mice Through Upregulation of Hedgehog Signaling",
  journal="JOURNAL OF BONE AND MINERAL RESEARCH",
  year="2021",
  volume="15",
  number="124",
  pages="1--17",
  doi="10.1002/jbmr.4427",
  issn="0884-0431",
  url="https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4427"
}