Transcription factors SP5 and SP8 drive primary cilia formation in mammalian embryos

• 成果类型: Article
• 署名作者: Liang, Yinwen; Koche, Richard; Chalamalasetty, Ravindra B.; Stephen, Daniel N.; Kennedy, Mark W.; Lao, Zhimin; Pang, Yunong; Kuo, Ying-Yi; Lee, Moonsup; Lobo, Francisco Pereira; Huang, Xiaofeng; Hadjantonakis, Anna-Katerina; Yamaguchi, Terry P.; Anderson, Kathryn V.; Joyner, Alexandra L.
• 署名单位: Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Cornell University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10098
• DOI: 10.1126/science.adt5663
• 发表日期: 2025-08-28
• 关键词: beta-catenin; factor rfx3; mouse; expression; ciliogenesis; motile; genes; cells; interacts; FAMILY

摘要

Although specific transcription factors (TFs) are known to regulate cell fate decisions, the degree to which they can stimulate formation of specific cell organelles is less clear. We used a multiomics comparison of the transcriptomes of ciliated and unciliated embryonic cells to identify TFs up-regulated in ciliated cells. We also used conditional genetics in mouse embryos and stem cells and found that the TFs SP5 and SP8 regulate cilia formation and gene expression. In embryos lacking Sp5 and Sp8, primary and motile cilia were shorter than normal and reduced in number across cell types, contributing to situs inversus and hydrocephalus. Moreover, expression of SP8 was sufficient to induce primary cilia in unciliated cells. This work will facilitate the study of cilia assembly using stem cell models and promote further understanding of human ciliopathies.