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@article{1383089,
author = {Bernatík, Ondřej and Radaszkiewicz, Tomasz Witold and Běhal, Martin and Dave, Zankruti and Witte, Florian and Mahl, Annika and Černohorská, Nicole and Krejčí, Pavel and Stricker, Sigmar and Bryja, Vítězslav},
article_location = {Lausanne},
article_number = {MAY},
doi = {http://dx.doi.org/10.3389/fcell.2017.00047},
keywords = {noggin; Wnt5a; non-canonical Wnt pathways; BMP signaling; brachydactyly; Ror2},
language = {eng},
issn = {2296-634X},
journal = {Frontiers in Cell and Developmental Biology},
title = {A Novel Role for the BMP Antagonist Noggin in Sensitizing Cells to Non-canonical Wnt-5a/Ror2/Disheveled Pathway Activation},
url = {http://dx.doi.org/10.3389/fcell.2017.00047},
volume = {5},
year = {2017}
}
TY - JOUR
ID - 1383089
AU - Bernatík, Ondřej - Radaszkiewicz, Tomasz Witold - Běhal, Martin - Dave, Zankruti - Witte, Florian - Mahl, Annika - Černohorská, Nicole - Krejčí, Pavel - Stricker, Sigmar - Bryja, Vítězslav
PY - 2017
TI - A Novel Role for the BMP Antagonist Noggin in Sensitizing Cells to Non-canonical Wnt-5a/Ror2/Disheveled Pathway Activation
JF - Frontiers in Cell and Developmental Biology
VL - 5
IS - MAY
SP - 1-9
EP - 1-9
PB - Frontiers Media S.A.
SN - 2296634X
KW - noggin
KW - Wnt5a
KW - non-canonical Wnt pathways
KW - BMP signaling
KW - brachydactyly
KW - Ror2
UR - http://dx.doi.org/10.3389/fcell.2017.00047
L2 - http://dx.doi.org/10.3389/fcell.2017.00047
N2 - Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway. Genetic analysis of Nog and Ror2 functional interaction via crossing Noggin and Ror2 mutant mice revealed a widening of skeletal elements in compound but not in any of the single mutants, thus indicating genetic interaction. Since ROR2 is a non-canonical Wnt co-receptor specific for Wnt-5a we speculated that this phenotype might be a result of deregulated Wnt-5a signaling activation, which is known to be essential for limb skeletal elements growth and patterning. We show that Noggin potentiates activation of the Wnt-5a-Ror2-Disheveled (Dvl) pathway in mouse embryonic fibroblast (MEF) cells in a Ror2-dependent fashion. Rat chondrosarcoma chondrocytes (RCS), however, are not able to respond to Noggin in this fashion unless growth arrest is induced by FGF2. In summary, our data demonstrate genetic interaction between Noggin and Ror2 and show that Noggin can sensitize cells to Wnt-5a/Ror2-mediated non-canonical Wnt signaling, a feature that in cartilage may depend on the presence of active FGF signaling. These findings indicate an unappreciated function of Noggin that will help to understand BMP and Wnt/PCP signaling pathway interactions.
ER -
BERNATÍK, Ondřej, Tomasz Witold RADASZKIEWICZ, Martin BĚHAL, Zankruti DAVE, Florian WITTE, Annika MAHL, Nicole ČERNOHORSKÁ, Pavel KREJČÍ, Sigmar STRICKER and Vítězslav BRYJA. A Novel Role for the BMP Antagonist Noggin in Sensitizing Cells to Non-canonical Wnt-5a/Ror2/Disheveled Pathway Activation. \textit{Frontiers in Cell and Developmental Biology}. Lausanne: Frontiers Media S.A., vol.~5, MAY, p.~1-9. ISSN~2296-634X. doi:10.3389/fcell.2017.00047. 2017.
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