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We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signal-regulated kinase (ERK)-specific MKP. Targeted inactivation of Dusp6 increases levels of phosphorylated ERK, as well as the pERK target, Erm, and transcripts initiated from the Dusp6 promoter itself. Finally, the Dusp6 mutant allele causes variably penetrant, dominant postnatal lethality, skeletal dwarfism,coronal craniosynostosis and hearing loss; phenotypes that are also characteristic of mutations that activate FGFRs inappropriately. Taken together, these results show that DUSP6 serves in vivo as a negative feedback regulator of FGFR signaling and suggest that mutations in DUSP6 or related genes are candidates for causing or modifying unexplained cases of FGFR-like syndromes.<\/jats:p>","DOI":"10.1242\/dev.02701","type":"journal-article","created":{"date-parts":[[2006,12,12]],"date-time":"2006-12-12T20:28:50Z","timestamp":1165955330000},"page":"167-176","source":"Crossref","is-referenced-by-count":265,"title":["<i>Dusp6<\/i>(<i>Mkp3<\/i>) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development"],"prefix":"10.1242","volume":"134","author":[{"given":"Chaoying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of Utah, 15 N 2030 E RM 2100, Salt Lake City, UT 84112-5330, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, 15 N 2030 E RM 2100, Salt Lake City, UT 84112-5330, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, 15 N 2030 E RM 2100, Salt Lake City, UT 84112-5330, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Tian","sequence":"additional","affiliation":[{"name":"Division of Radiobiology, University of Utah, 729 Arapeen Drive #2334, Salt Lake City, UT 84108-1218, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, 15 N 2030 E RM 2100, Salt Lake City, UT 84112-5330, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042612163384700_REF1","doi-asserted-by":"crossref","unstructured":"Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Friedberg,I., Osterman, A., Godzik, A., Hunter, T., Dixon, J. and Mustelin, T.(2004). 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