title: Sufu and Kif7 in limb patterning and development.
abstract: BACKGROUND
  The vertebrate digit pattern is defined by the morphogen Sonic hedgehog (Shh), which controls the activity of Gli transcription factors. Gli1, 2 and 3 are dynamically expressed during patterning. Downstream of Shh, their activity is regulated by Sufu and Kif7, core components of the Shh signaling cascade. The precise roles of these regulators during limb development have not been fully described. We analyze the role of Sufu and Kif7 in the limb and demonstrate that their loss has distinct and synergistic effects on Gli activity and digit pattern.
  
  
  RESULTS
  Using a series of mouse mutants, we show that Sufu and Kif7 are expressed throughout limb development and their deletion has distinct effects on Gli levels and limb formation. Concomitant deletion of Sufu and Kif7 results in constitutive pathway activity and severe limb truncation. This is consistent with the recently published two-population model, which suggests that precocious activation of Shh signaling inhibits organizing center formation and limb outgrowth.
  
  
  CONCLUSIONS
  Together, our findings demonstrate that perturbations of Sufu and Kif7 affect Gli activity and recapitulate the full spectrum of vertebrate limb defects, ranging from severe truncation to polydactyly.
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Olena
authors.initials: O
authors.lastname: Zhulyn
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb / Q000196:embryology*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D017689:Polydactyly / Q000196:embryology / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D012097:Repressor Proteins; C465570:Shh protein, mouse; C490763:Sufu protein, mouse; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; C543639:Kif7 protein, mouse; D016547:Kinesins
keywords: Gli transcription factors; Kif7; Sonic hedgehog; Sufu; limb patterning; two-population model