DSpace

Digital.CSIC > Biología y Biomedicina > Instituto de Neurociencias (IN) > (IN) Artículos >

Share

EndNote

Impact

Links

Closed Access item Snail1 Is a Transcriptional Effector of FGFR3 Signaling during Chondrogenesis and Achondroplasias

Authors:Frutos, Cristina A. de
Vega, Sonia
Manzanares, Miguel
Flores, Juana María
Huertas, Héctor
Martínez-Frías, María Luisa
Nieto, M. Ángela
Issue Date:4-Dec-2007
Publisher:Elsevier
Citation:Developmental Cell 13(6): 872-883 (2007)
Abstract:Achondroplasias are the most common genetic forms of dwarfism in humans. They are associated with activating mutations in FGFR3, which signal through the Stat and MAPK pathways in a ligand-independent manner to impair chondrocyte proliferation and differentiation. Snail1 has been implicated in chondrocyte differentiation as it represses Collagen II and aggrecan transcription in vitro. Here we demonstrate that Snail1 overexpression in the developing bone leads to achondroplasia in mice. Snail1 acts downstream of FGFR3 signaling in chondrocytes, regulating both Stat and MAPK pathways. Moreover, FGFR3 requires Snail1 during bone development and disease as the inhibition of Snail1 abolishes its signaling even through achondroplastic- and thanatophoric-activating FGFR3 forms. Significantly, Snail1 is aberrantly upregulated in thanatophoric versus normal cartilages from stillborns. Thus, Snail activity may likely be considered a target for achondroplasia therapies.
Description:12 páginas, 7 figuras.
Publisher version (URL):http://dx.doi.org/10.1016/j.devcel.2007.09.016
URI:http://hdl.handle.net/10261/32379
ISSN:1534-5807
???metadata.dc.identifier.doi???:10.1016/j.devcel.2007.09.016
Appears in Collections:(IN) Artículos
(IIBM) Artículos

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.