| BOSÁKOVÁ, Michaela, Miroslav VAŘECHA, Marek HAMPL, Ivan DURAN, Alexandru NITĂ, Marcela BUCHTOVÁ, Hana DOSEDELOVA, Radek MACHÁT, Yangli XIE, Zhenhong NI, Jorge H. MARTIN, Lin CHEN, Gert JANSEN, Deborah KRAKOW and Pavel KREJČÍ. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies. Human molecular genetics. OXFORD: OXFORD UNIV PRESS, 2018, vol. 27, No 6, p. 1093-1105. ISSN 0964-6906. Available from: https://dx.doi.org/10.1093/hmg/ddy031. |
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@article{1490536,
author = {Bosáková, Michaela and Vařecha, Miroslav and Hampl, Marek and Duran, Ivan and Nită, Alexandru and Buchtová, Marcela and Dosedelova, Hana and Machát, Radek and Xie, Yangli and Ni, Zhenhong and Martin, Jorge H. and Chen, Lin and Jansen, Gert and Krakow, Deborah and Krejčí, Pavel},
article_location = {OXFORD},
article_number = {6},
doi = {http://dx.doi.org/10.1093/hmg/ddy031},
keywords = {ciliary function; fibroblast growth factor; FGFR3},
language = {eng},
issn = {0964-6906},
journal = {Human molecular genetics},
title = {Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies},
url = {https://academic.oup.com/hmg/article/27/6/1093/4816205},
volume = {27},
year = {2018}
}
TY - JOUR
ID - 1490536
AU - Bosáková, Michaela - Vařecha, Miroslav - Hampl, Marek - Duran, Ivan - Nită, Alexandru - Buchtová, Marcela - Dosedelova, Hana - Machát, Radek - Xie, Yangli - Ni, Zhenhong - Martin, Jorge H. - Chen, Lin - Jansen, Gert - Krakow, Deborah - Krejčí, Pavel
PY - 2018
TI - Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies
JF - Human molecular genetics
VL - 27
IS - 6
SP - 1093-1105
EP - 1093-1105
PB - OXFORD UNIV PRESS
SN - 09646906
KW - ciliary function
KW - fibroblast growth factor
KW - FGFR3
UR - https://academic.oup.com/hmg/article/27/6/1093/4816205
N2 - 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.
ER -
BOSÁKOVÁ, Michaela, Miroslav VAŘECHA, Marek HAMPL, Ivan DURAN, Alexandru NIT$\backslash$U A, Marcela BUCHTOVÁ, Hana DOSEDELOVA, Radek MACHÁT, Yangli XIE, Zhenhong NI, Jorge H. MARTIN, Lin CHEN, Gert JANSEN, Deborah KRAKOW and Pavel KREJČÍ. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies. \textit{Human molecular genetics}. OXFORD: OXFORD UNIV PRESS, 2018, vol.~27, No~6, p.~1093-1105. ISSN~0964-6906. Available from: https://dx.doi.org/10.1093/hmg/ddy031.
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