ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling

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• dc.contributor.author Handschuh, Karen
• dc.contributor.author Quintana, Laura
• dc.contributor.author Sharpe, James
• dc.contributor.author Selleri, Licia
• dc.date.accessioned 2024-01-22T06:50:05Z
• dc.date.available 2024-01-22T06:50:05Z
• dc.date.issued 2014
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Sorting and degradation of receptors and associated signaling molecules maintain homeostasis of conserved signaling pathways during cell specification and tissue development. Yet, whether machineries that sort signaling proteins act preferentially on different receptors and ligands in different contexts remains mysterious. Here, we show that Vacuolar protein sorting 25, Vps25, a component of ESCRT-II (Endosomal Sorting Complex Required for Transport II), directs preferential endosome-mediated modulation of FGF signaling in limbs. By ENU-induced mutagenesis, we isolated a polydactylous mouse line carrying a hypomorphic mutation of Vps25 (Vps25ENU). Unlike Vps25-null embryos we generated, Vps25ENU/ENU mutants survive until late gestation. Their limbs display FGF signaling enhancement and consequent hyperactivation of the FGF-SHH feedback loop causing polydactyly, whereas WNT and BMP signaling remain unperturbed. Notably, Vps25ENU/ENU Mouse Embryonic Fibroblasts exhibit aberrant FGFR trafficking and degradation; however, SHH signaling is unperturbed. These studies establish that the ESCRT-II machinery selectively limits FGF signaling in vertebrate skeletal patterning.
• dc.format.mimetype application/pdf
• dc.identifier.citation Handschuh K, Feenstra J, Koss M, Ferretti E, Risolino M, Zewdu R, et al. ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling. Cell Reports. 2014 Oct 23;9(2):674-87. DOI: 10.1016/j.celrep.2014.09.019
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2014.09.019
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/58774
• dc.language.iso eng
• dc.publisher Cell Press
• dc.relation.ispartof Cell Reports. 2014 Oct 23;9(2):674-87
• dc.rights This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/3.0/
• dc.subject.other Homeòstasi
• dc.subject.other Cèl·lules
• dc.subject.other Ratolins
• dc.title ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion