title: The FgfrL1 receptor is required for development of slow muscle fibers.
abstract: FgfrL1, which interacts with Fgf ligands and heparin, is a member of the fibroblast growth factor receptor (Fgfr) family. FgfrL1-deficient mice show two significant alterations when compared to wildtype mice: They die at birth due to a malformed diaphragm and they lack metanephric kidneys. Utilizing gene arrays, qPCR and in situ hybridization we show here that the diaphragm of FgfrL1 knockout animals lacks any slow muscle fibers at E18.5 as indicated by the absence of slow fiber markers Myh7, Myl2 and Myl3. Similar lesions are also found in other skeletal muscles that contain a high proportion of slow fibers at birth, such as the extraocular muscles. In contrast to the slow fibers, fast fibers do not appear to be affected as shown by expression of fast fiber markers Myh3, Myh8, Myl1 and MylPF. At early developmental stages (E10.5, E15.5), FgfrL1-deficient animals express slow fiber genes at normal levels. The loss of slow fibers cannot be attributed to the lack of kidneys, since Wnt4 knockout mice, which also lack metanephric kidneys, show normal expression of Myh7, Myl2 and Myl3. Thus, FgfrL1 is specifically required for embryonic development of slow muscle fibers.
authors.affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Amann
authors.affiliation: Institute of Plant Biology, University of Zurich, 8008 Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wyder
authors.affiliation: Department of Pediatrics, University of California, San Francisco, CA 94143-0748, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Slavotinek
authors.affiliation: Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Rheumatology, University Hospital, 3010 Bern, Switzerland. Electronic address: beat.trueb@dkf.unibe.ch.
authors.forename: Beat
authors.initials: B
authors.lastname: Trueb
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D003964:Diaphragm / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D024510:Muscle Development / Q000235:genetics* / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051500:Receptor, Fibroblast Growth Factor, Type 5 / Q000378:metabolism*
chemical_list: C496379:Fgfrl1 protein, mouse; C551613:Myh7 protein, mouse; C484588:Myl1 protein, mouse; C521958:Mylpf protein, mouse; D018994:Myosin Light Chains; D051500:Receptor, Fibroblast Growth Factor, Type 5; D018995:Myosin Heavy Chains
keywords: Diaphragm; Extraocular muscles; Fgfr; FgfrL1; Fibroblast growth factor; Fibroblast growth factor receptor; Muscle development; Slow muscle fibers