title: Hedgehog signaling patterns the outgrowth of unpaired skeletal appendages in zebrafish.
abstract: BACKGROUND
  Little is known about the control of the development of vertebrate unpaired appendages such as the caudal fin, one of the key morphological specializations of fishes. Recent analysis of lamprey and dogshark median fins suggests the co-option of some molecular mechanisms between paired and median in Chondrichthyes. However, the extent to which the molecular mechanisms patterning paired and median fins are shared remains unknown.
  
  
  RESULTS
  Here we provide molecular description of the initial ontogeny of the median fins in zebrafish and present several independent lines of evidence that Sonic hedgehog signaling emanating from the embryonic midline is essential for establishment and outgrowth of the caudal fin primordium. However, gene expression analysis shows that the primordium of the adult caudal fin does not harbor a Sonic hedgehog-expressing domain equivalent to the Shh secreting zone of polarizing activity (ZPA) of paired appendages.
  
  
  CONCLUSIONS
  Our results suggest that Hedgehog proteins can regulate skeletal appendage outgrowth independent of a ZPA and demonstrates an unexpected mechanism for mediating Shh signals in a median fin primordium. The median fins evolved before paired fins in early craniates, thus the patterning of the median fins may be an ancestral mechanism that controls the outgrowth of skeletogenic appendages in vertebrates.
authors.affiliation: Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Karlsruhe, Germany. yavor.hadzhiev@itg.fzk.de <yavor.hadzhiev@itg.fzk.de>
authors.forename: Yavor
authors.initials: Y
authors.lastname: Hadzhiev
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lele
authors.forename: Simone
authors.initials: S
authors.lastname: Schindler
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
authors.forename: Per
authors.initials: P
authors.lastname: Ahlberg
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
authors.forename: Ferenc
authors.initials: F
authors.lastname: Müller
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D018878:Limb Buds / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; C000541:cyclopamine