title: Mouse pigpen encodes a nuclear protein whose expression is developmentally regulated during craniofacial morphogenesis.
abstract: Pigpen, a nuclear protein with RNA-binding motifs and a putative transcriptional activation domain (TAD), is expressed at high levels in proliferating endothelial cells and expression is down-regulated when cells adopt a quiescent or differentiated phenotype. We cloned the mouse homolog of pigpen and investigated the regulation of its expression during embryogenesis. In situ hybridization demonstrated that a broad pattern of pigpen expression became restricted during tooth formation in the mandible. In the eye, pigpen showed a spatial restriction to the more proliferating and less differentiated regions of the lens and neural retina. Expression was also restricted in the developing vibrissae, lung, and kidney, all sites where epithelial-mesenchymal interactions are vital for morphogenesis. In vitro assays, that focused on the mandible and tooth development, indicated that epithelial signals, mediated by fibroblast growth factor-8, were required to maintain pigpen expression in the mandibular mesenchyme, whereas bone morphogenetic protein-4 negatively regulated expression in that tissue during early odontogenesis. At the protein level, immunocytochemistry demonstrated that Pigpen was expressed diffusely in the cytoplasm and more concentratedly in focal granules within the nuclei of mouse embryonic cells. Lastly, CAT reporter assays showed that the N-terminus of mouse pigpen encodes an active TAD. These data suggest that mouse Pigpen may activate transcription in vivo in response to specific growth factor signals and regulate proliferation and/or differentiation events during mouse organogenesis.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, USA. salappa@tulane.edu
authors.forename: Sylvia R
authors.initials: SR
authors.lastname: Alappat
authors.forename: Meifeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Alliegro
authors.forename: Mark C
authors.initials: MC
authors.lastname: Alliegro
authors.forename: Carol A
authors.initials: CA
authors.lastname: Burdsal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005145:Face / Q000196:embryology*; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007568:Jaw / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012886:Skull / Q000196:embryology*; D018243:Teratocarcinoma / Q000473:pathology; D014070:Tooth / Q000196:embryology
chemical_list: D019485:Bone Morphogenetic Proteins; C496457:Fgf8 protein, mouse; D009687:Nuclear Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors