A tissue-specific role for intraflagellar transport genes during craniofacial development

• Published in: PloS one Vol. 12; no. 3; p. e0174206
• Main Authors: Schock, Elizabeth N, Struve, Jaime N, Chang, Ching-Fang, Williams, Trevor J, Snedeker, John, Attia, Aria C, Stottmann, Rolf W, Brugmann, Samantha A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.03.2017; Public Library of Science (PLoS)
• Subjects: Aberration; Ablation; Adaptor Proteins, Signal Transducing - genetics; AKT protein; Animal models; Animals; Arrestin; Basal bodies; Biology; Biology and Life Sciences; Bone growth; Cargo; Cell death; Cell surface; Children; Cilia; Cilia - genetics; Combinatorial analysis; Cranial sutures; Craniofacial abnormalities; Craniofacial Abnormalities - genetics; Craniosynostosis; Defects; Developmental biology; Diagnosis; Differentiation; Disorders; Division; Embryos; Endochondral bone; Etiology; Face - abnormalities; Face - embryology; Female; Fibroblasts; Gene Deletion; Gene expression; Gene Expression Regulation, Developmental; Genes; Genetic aspects; Genetics; Heart; Hospitals; Hyperplasia; Kinesins - genetics; Liver diseases; Male; Mammals; Medicine and Health Sciences; Mice; Morphogenesis; Movement disorders; Mutants; Mutation; Neural Crest - embryology; Neural Crest - metabolism; Neural Plate - embryology; Neural Plate - metabolism; Neurodegenerative diseases; Parkinson's disease; Pediatrics; Physiological aspects; Plastic surgery; Position (location); Proteins; Retinitis pigmentosa; Septum; Skull; Skull - abnormalities; Skull - embryology; Skull - metabolism; Surgery; Tissues; Transcription factors; Tumor Suppressor Proteins - genetics; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174206

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.