Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F18%3A00101656" target="_blank" >RIV/00216224:14110/18:00101656 - isvavai.cz</a>

Alternative codes found

RIV/67985904:_____/18:00489556 RIV/00159816:_____/18:00068658

Result on the web

<a href="http://dx.doi.org/10.1093/hmg/ddy031" target="_blank" >http://dx.doi.org/10.1093/hmg/ddy031</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/hmg/ddy031" target="_blank" >10.1093/hmg/ddy031</a>

Result language

angličtina

Original language name

Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies

Original language description

Cilia project from almost every cell integrating extracellular cues with signaling pathways. Constitutive activation of FGFR3 signaling produces the skeletal disorders achondroplasia (ACH) and thanatophoric dysplasia (TD), but many of the molecular mechanisms underlying these phenotypes remain unresolved. Here, we report in vivo evidence for significantly shortened primary cilia in ACH and TD cartilage growth plates. Using in vivo and in vitro methodologies, our data demonstrate that transient versus sustained activation of FGF signaling correlated with different cilia consequences. Transient FGF pathway activation elongated cilia, while sustained activity shortened cilia. FGF signaling extended primary cilia via ERK MAP kinase and mTORC2 signaling, but not through mTORC1. Employing a GFP-tagged IFT20 construct to measure intraflagellar (IFT) speed in cilia, we showed that FGF signaling affected IFT velocities, as well as modulating cilia-based Hedgehog signaling. Our data integrate primary cilia into canonical FGF signal transduction and uncover a FGF-cilia pathway that needs consideration when elucidating the mechanisms of physiological and pathological FGFR function, or in the development of FGFR therapeutics.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

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)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Human molecular genetics

ISSN

0964-6906

e-ISSN

1460-2083

Volume of the periodical

27

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

1093-1105

UT code for WoS article

000426838700013

EID of the result in the Scopus database

2-s2.0-85043313766