Journal Article

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

Snedeker, John, Stottmann, Rolf W., Williams, Trevor J., Chang, Ching-Fang, Struve, Jaime N., Attia, Aria C., Schock, Elizabeth N., Brugmann, Samantha A.

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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