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

   

Authors:	Handschuh, K.; Feenstra, J.; Koss, M.; Ferretti, E.; Risolino, M.; Zewdu, R.; Sahai, M. A.; Bénazet, J. D.; Peng, X. P.; Depew, M. J.; Quintana, L.; Sharpe, J.; Wang, B.; Alcorn, H.; Rivi, R.; Butcher, S.; Robert Manak, J.; Vaccari, T.; Weinstein, H.; Anderson, K. V.; Lacy, E.; Selleri, L.
Article Title:	ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling
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.
Keywords:	vertebrata
Journal Title:	Cell Reports
Volume:	9
Issue:	2
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2014-10-23
Start Page:	674
End Page:	687
Language:	English
DOI:	10.1016/j.celrep.2014.09.019
PROVIDER:	scopus
PMCID:	PMC4223648
PUBMED:	25373905
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84919675156&partnerID=40&md5=a43927c5b18e1874bba018517b422001
Notes:	Export Date: 2 January 2015 -- Source: Scopus

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