SP5 and SP8 transcription factors drive primary cilia formation in early embryo

ABSTRACT: Primary cilia play critical roles in sensory and signaling functions, and their dysregulation is associated with developmental abnormalities and multi-organ diseases. Despite their importance, the transcriptional regulation of primary cilia genes is unclear. Here, we employed transcriptome and mouse genetic tools to identify a master regulator of primary cilia genes. By comparing ciliated and non-ciliated cells in the early embryo using scRNA-seq and ChIP-seq, we uncovered that a wide spectrum of primary cilia genes are upregulated in ciliated cells and that SP5/8 within the SP/KLF family of transcription factors bind a core set of cilia genes. Loss- and gain-of-function assays in mouse embryos and embryonic stem cells demonstrate Sp5/8, are required for the initial formation of primary cilia in all embryonic cell types. Moreover, Sp5/8 loss compromises the formation of the more specialized motile cilia present in the embryonic node. Finally, misexpression of SP8 is sufficient to induce primary cilia formation in two unciliated cell types. Our findings demonstrate that SP5/8 are essential for cilia initiation in the embryo and sufficient to drive cilia formation in unciliated cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE274844 | GEO | 2025/06/25

REPOSITORIES: GEO