Cilia and transcription: a mini review

Abstract

Cilia assembly is accompanied by rapid and highly coordinated transcription of hundreds of genes. Cilia gene regulation has been studied extensively in both metazoans and unicellular model organisms. The forkhead and RFX family transcription factors regulating cilia genes in animals were first identified 25 years ago and considerable molecular details of the regulatory processes have been described since then. While many of the most important early studies of cilia gene regulation were done in unicellular organisms, additional molecular players need to be discovered for a more complete understanding in these organisms. In this concise review, written primarily for students new to the field, I present a brief history of research on cilia gene regulation, highlight some key metazoan discoveries from the last decade, and discuss gaps in our understanding of cilia gene regulation in unicellular model organisms with a focus on Chlamydomonas reinhardtii.

Keywords: Chlamydomonas; FoxJ1; RFX; XAP5; cilia; flagella; gene regulation; transcription.

FIGURE 1

Multiciliated cell differentiation. (A) Mammalian respiratory epithelium including MCC interspersed with secretory cells. (B) Regulation of MCC development. A complex containing GEMC1 and the E2F5 and p73 transcription factors activates p73 as well as MCIDAS and the FOXJ1, RFX2 and RFX3 ciliogenesis transcription factors. MCIDAS in complex with E2F4 or E2F5 also activates FOXJ1, RFX2, and RFX3 and promotes centriole expansion. FOXJ1 promotes basal body docking and activates expression of axonemal proteins required for cilia motility. RFX2 and RFX3 activate the expression of many cilia genes needed for assembly of all cilia including the motile cilia on MCC. Notch signaling blocks GEMC1 complex activation leading to a secretory cell fate (Lalioti et al., 2019; Lewis and Stracker, 2021; Lu et al., 2019). Created in BioRender. Brown, (2025) https://BioRender.com/z01l282.

FIGURE 2

Gene regulation during cilia regeneration in Chlamydomonas. (A) Different temporal expression patterns and XAP5. Cilia genes are expressed in groups with different expression patterns. Depicted here are early (squares) middle (circles) and late (triangle) genes (Schloss et al., 1984). In addition, nuclear localized XAP5 is phosphorylated rapidly after deciliation by an unidentified kinase. (B) Calcium involvement in cilia gene induction. Upon pH shock, extracellular calcium enters the cell and stimulates the release of additional calcium from intracellular stores and triggers deciliation (Quarmby and Mahjoub, 2023). Calcium entry is needed for maximal gene induction concomitant with the initiation of cilia regrowth (Cheshire and Keller, 1991). How the intracellular calcium concentration changes are involved in normal gene induction is still unclear. (C) The repressor sequestration model. A constitutively produced repressor (stars) blocks cilia gene expression. After deciliation, the repressor is sequestered in rapidly growing cilia, reducing the effective concentration of the repressor in the cell body and allowing increased transcription of cilia genes. As cilia approach full length, cilia assembly slows down allowing the repressor to accumulate and cilia gene expression to slow down (Perlaza et al., 2023).