title: Prickle1 stunts limb growth through alteration of cell polarity and gene expression.
abstract: BACKGROUND
  Wnt/PCP signaling plays a critical role in multiple developmental processes, including limb development. Wnt5a, a ligand of the PCP pathway, signals through the Ror2/Vangl2 or the Vangl2/Ryk complex to regulate limb development along the proximal-distal axis in mice. Based on the interaction between Van Gogh and Prickle in Drosophila, we hypothesized the vertebrate Prickle1 has a similar function as Vangl2 in limb development.
  
  
  RESULTS
  We show Prickle1 is expressed in the skeletal condensates that will differentiate into chondrocytes and later form bones. Disrupted Prickle1 function in Prickle1(C251X/C251X) mouse mutants alters expression of genes such as Bmp4, Fgf8, Vangl2, and Wnt5a. These expression changes correlate with shorter and wider bones in the limbs and loss of one phalangeal segment in digits 2-5 of Prickle1C251X mutants. These growth defects along the proximal-distal axis are also associated with increased cell death in the growing digit tip, reduced cell death in the interdigital membrane, and disrupted chondrocyte polarity.
  
  
  CONCLUSIONS
  We suggest Prickle1 is part of the Wnt5a/PCP signaling, regulating cell polarity and affecting expression of multiple factors to stunt limb growth through altered patterns of gene expression, including the PCP genes Wnt5a and Vangl2.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bassuk
authors.forename: Bernd
authors.initials: B
authors.lastname: Fritzsch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C496457:Fgf8 protein, mouse; D060588:LIM Domain Proteins; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; C524253:Prickle1 protein, mouse; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D051524:Fibroblast Growth Factor 8
keywords: Prickle1; chondrocyte polarity; limb growth
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