title: A tissue-specific role for intraflagellar transport genes during craniofacial development.
abstract: Primary cilia are nearly ubiquitous, cellular projections that function to transduce molecular signals during development. Loss of functional primary cilia has a particularly profound effect on the developing craniofacial complex, causing several anomalies including craniosynostosis, micrognathia, midfacial dysplasia, cleft lip/palate and oral/dental defects. Development of the craniofacial complex is an intricate process that requires interactions between several different tissues including neural crest cells, neuroectoderm and surface ectoderm. To understand the tissue-specific requirements for primary cilia during craniofacial development we conditionally deleted three separate intraflagellar transport genes, Kif3a, Ift88 and Ttc21b with three distinct drivers, Wnt1-Cre, Crect and AP2-Cre which drive recombination in neural crest, surface ectoderm alone, and neural crest, surface ectoderm and neuroectoderm, respectively. We found that tissue-specific conditional loss of ciliary genes with different functions produces profoundly different facial phenotypes. Furthermore, analysis of basic cellular behaviors in these mutants suggests that loss of primary cilia in a distinct tissue has unique effects on development of adjacent tissues. Together, these data suggest specific spatiotemporal roles for intraflagellar transport genes and the primary cilium during craniofacial development.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.|Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Elizabeth N
authors.identifier: http://orcid.org/0000-0002-3970-799X
authors.initials: EN
authors.lastname: Schock
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.|Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Jaime N
authors.initials: JN
authors.lastname: Struve
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.|Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Department of Craniofacial Biology, University of Colorado School of Dental Medicine, Aurora, Colorado, United States of America.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Williams
authors.affiliation: Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Snedeker
authors.affiliation: Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Aria C
authors.identifier: http://orcid.org/0000-0002-1666-5395
authors.initials: AC
authors.lastname: Attia
authors.affiliation: Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.|Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Rolf W
authors.identifier: http://orcid.org/0000-0003-4512-6806
authors.initials: RW
authors.lastname: Stottmann
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.|Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brugmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D002923:Cilia / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D005145:Face / Q000002:abnormalities / Q000196:embryology*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins / Q000235:genetics; D008297:Male; D051379:Mice; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D012886:Skull / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490202:Kif3a protein, mouse; C490898:Tg737Rpw protein, mouse; C528451:Ttc21b protein, mouse; D025521:Tumor Suppressor Proteins; D016547:Kinesins