title: Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice.
abstract: Previous in vitro studies have indicated multiple and varied roles of Pinin (PNN); however, its in vivo role has remained unclear. Here, we report generation of null, hypomorphic, and conditional Pnn alleles in mice. We found that insertion of neomycin-resistance cassette into intron 8 of Pnn resulted in knockdown of Pnn, which allowed Pnn hypomorphic embryos to pass peri-implantation lethality. These mice are lethal at perinatal stages and exhibit defects in the cardiac outflow tract, palate, dorsal dermis, and axial skeleton. Since Wnt/beta-catenin signaling has been shown to play pivotal roles in development of all tissues affected by Pnn hypomorphism, we speculated that Pnn may affect Wnt/beta-catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in beta-catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pnn plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity.
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Joo
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Munguba
authors.forename: Sean
authors.initials: S
authors.lastname: Park
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Taxter
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Elsagga
authors.forename: Moira R
authors.initials: MR
authors.lastname: Jackson
authors.forename: S Paul
authors.initials: SP
authors.lastname: Oh
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Sugrue
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D020405:Dermis / Q000196:embryology* / Q000254:growth & development; D004628:Embryonic Structures; D051379:Mice; D009432:Neural Crest / Q000196:embryology* / Q000254:growth & development; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012863:Skeleton; D051820:TCF Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000032:analysis
chemical_list: D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C491175:Pnn protein, mouse; D051820:TCF Transcription Factors; D051176:beta Catenin