Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

Primary cilia are nearly ubiquitous organelles that transduce molecular and mechanical signals. Although the basic structure of the cilium and the cadre of genes that contribute to ciliary formation and function (the ciliome) are believed to be evolutionarily conserved, the presentation of ciliopathies with narrow, tissue-specific phenotypes and distinct molecular readouts suggests that an unappreciated heterogeneity exists within this organelle. Here, we provide a searchable transcriptomic resource for a curated primary ciliome, detailing various subgroups of differentially expressed genes within the ciliome that display tissue and temporal specificity. Genes within the differentially expressed ciliome exhibited a lower level of functional constraint across species, suggesting organism and cellspecific function adaptation. The biological relevance of ciliary heterogeneity was functionally validated by using Cas9 geneediting to disrupt ciliary genes that displayed dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Collectively, this novel primary cilia-focused resource will allow researchers to explore longstanding questions related to how tissue and cell-type specific functions and ciliary heterogeneity may contribute to the range of phenotypes associated with ciliopathies.

Automated summary

This study provides a searchable transcriptomic resource for the primary ciliome, revealing differentially expressed genes with tissue and temporal specificity. The genes within the differentially expressed ciliome show a lower level of functional constraint across species, indicating organism and cell-specific functional adaptation. The functional validation of ciliary heterogeneity was performed by disrupting ciliary genes using Cas9 gene editing, which exhibited dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Overall, this novel primary cilia-focused resource allows researchers to explore the correlation between tissue and cell-type specific functions, ciliary heterogeneity, and the range of phenotypes associated with ciliopathies.