title: Identification of evolutionarily conserved regulatory elements in the mouse Fgf8 locus.
abstract: The secreted signaling molecule fibroblast growth factor 8 (Fgf8) is an essential component of certain embryonic signaling centers including the mid-hindbrain (isthmic) organizer, the first branchial arch (BA1), and the apical ectodermal ridge (AER). In these signaling centers Fgf8 transcripts are expressed in a dynamic and transient fashion, but the mechanism by which this highly specific expression pattern is established remains largely unknown. We used DNA sequence comparisons coupled to transgenic approaches to obtain insight into the structure and function of regulatory elements in the Fgf8 locus. First, a bacterial artificial chromosome (BAC) containing the mouse Fgf8 gene partially rescues the embryonic lethality of Fgf8-deficient mice and controls Fgf8-specific gene expression of a coinjected lacZ reporter transgene. Second, sequence comparison of vertebrate Fgf8 loci revealed evolutionarily highly conserved noncoding sequences that were unexpectedly located mainly 3' of the Fgf8 coding region. Third, in transgenic mice some of these elements were sufficient to target expression to the AER, tail bud, and brain, including the isthmic organizer, indicating that they may represent Fgf8 cis-acting elements. Collectively, these data identify novel regulatory elements of the Fgf8 gene sufficient to drive expression to regions of known Fgf8 activity.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Kostas
authors.initials: K
authors.lastname: Kaloulis
authors.forename: Denise
authors.initials: D
authors.lastname: Hofmann
authors.forename: Fabien
authors.initials: F
authors.lastname: Murisier
authors.forename: Philipp
authors.initials: P
authors.lastname: Bucher
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D051524:Fibroblast Growth Factor 8 / Q000235:genetics*; D020868:Gene Silencing; D051379:Mice; D008822:Mice, Transgenic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D017931:DNA Primers; C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8