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.
Highlights
Primary cilia are ubiquitous, microtubule-based extensions that protrude off a plethora of cell types throughout development
Tissue specific Cre-drivers allow for conditional knockout of ciliary genes in the tissues that contribute to the craniofacial complex
The developing surface ectoderm houses many signaling centers that are important for directing craniofacial development such as the frontonasal ectodermal zone (FEZ) and the nasal pits [23,24,25,26,27]
Summary
Microtubule-based extensions that protrude off a plethora of cell types throughout development. There is no established phenotypic criterion for diagnosis of a ciliopathy, it has been hypothesized that a ciliopathy
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