title: Functions of FGF signalling from the apical ectodermal ridge in limb development.
abstract: To determine the role of fibroblast growth factor (FGF) signalling from the apical ectodermal ridge (AER), we inactivated Fgf4 and Fgf8 in AER cells or their precursors at different stages of mouse limb development. We show that FGF4 and FGF8 regulate cell number in the nascent limb bud and are required for survival of cells located far from the AER. On the basis of the skeletal phenotypes observed, we conclude that these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other limb tissues. In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival.
authors.affiliation: Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, 94143-0452, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Mariani
authors.forename: Gail R
authors.initials: GR
authors.lastname: Martin
mesh_terms: D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D002452:Cell Count; D002455:Cell Division; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005552:Forelimb / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018878:Limb Buds / Q000166:cytology / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
chemical_list: C496457:Fgf8 protein, mouse; C112971:fibroblast growth factor 14; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors