An ancient transcription factor functions as the master regulator of primary cilia formation
Wang, W.; Zhang, X.; Qiu, Y.; Meng, X.; Cheng, S.; Chen, Y.; liu, S.; Chen, W.; Yi, J.; You, X.; Liu, H.; Xing, J.; Xu, C.; Jiang, H.; Wang, H.; Tian, G.; Hu, Z.
Show abstract
How ancient transcription factors are repurposed during evolution to drive the functional diversification of conserved organelles remains a fundamental question in biology. Although highly conserved in basic morphology, eukaryotic cilia vary extensively in their sizes and functions. Previously, we showed that an evolutionarily ancient transcription factor, X chromosome-associated protein 5 (Xap5), controls motile ciliogenic transcriptional programs during mouse spermatogenesis (Wang et al., 2025). Here we show that Xap5 functions as the master regulator of primary ciliogenesis. Xap5 associates with the nuclear protein Non-POU domain-containing octamer-binding protein (Nono) to form a regulatory module that directly binds and activates the transcription factors Sox5 and Sox9. Genetic ablation of Xap5 or Nono impairs primary ciliogenesis, and loss of Sox5 disrupts the downstream ciliogenic program, consistent with the established role of Sox9. Collectively, our results provide new insight into how complex ciliary transcription factor networks determine ciliary diversity during evolution, and suggest that defects in this regulatory axis may contribute to the etiology of human ciliopathies.
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