title: Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb.
abstract: Crosstalk between the fibroblast growth factor (FGF) and Sonic Hedgehog (Shh) pathways is critical for proper patterning and growth of the developing limb bud. Here, we show that FGF-dependent activation of the ETS transcription factors Etv4 and Etv5 contributes to proximal-distal limb outgrowth. Surprisingly, blockage of Etv activity in early distal mesenchyme also resulted in ectopic, anterior expansion of Shh, leading to a polydactylous phenotype. These data indicate an unexpected function for an FGF/Etv pathway in anterior-posterior patterning. FGF activity in the limb is not only responsible for maintaining posterior-specific Shh expression, but it also acts via Etvs to prevent inappropriate anterior expansion of Shh. This study identifies another level of genetic interaction between the orthogonal axes during limb development.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Junhao
authors.initials: J
authors.lastname: Mao
authors.forename: Edwina
authors.initials: E
authors.lastname: McGlinn
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
mesh_terms: D000818:Animals; D019521:Body Patterning; D016764:Cell Polarity; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004475:Ectoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D051761:Paired Box Transcription Factors / Q000378:metabolism; D017689:Polydactyly / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014714:Vertebrates / Q000196:embryology*
chemical_list: D004268:DNA-Binding Proteins; C540571:Etv4 protein, mouse; C513242:Etv5 protein, mouse; C496457:Fgf8 protein, mouse; D053823:Hedgehog Proteins; D051761:Paired Box Transcription Factors; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; C465570:Shh protein, mouse; D014157:Transcription Factors; C101485:homeobox protein PITX1; D051524:Fibroblast Growth Factor 8; C045073:Cre recombinase; D019426:Integrases