Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in C. elegans
- Instituto de Biomedicina de Valencia, Spain
- Karolinska Institute, Sweden
- Centro Andaluz de Biología del Desarrollo, Spain
Abstract
Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionarily conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome. Ciliome gene mutations underlie a group of pleiotropic genetic diseases known as ciliopathies. Proper cilium function requires the tight coregulation of ciliome gene transcription, which is only fragmentarily understood. RFX transcription factors (TF) have an evolutionarily conserved role in the direct activation of ciliome genes both in motile and non-motile cilia cell-types. In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types. No additional TFs have been described to act together with RFX in primary cilia cell-types in any organism. Here we describe FKH-8, a FKH TF, as a direct regulator of the sensory ciliome genes in Caenorhabditis elegans. FKH-8 is expressed in all ciliated neurons in C. elegans, binds the regulatory regions of ciliome genes, regulates ciliome gene expression, cilium morphology and a wide range of behaviours mediated by sensory ciliated neurons. FKH-8 and DAF-19 (C. elegans RFX) physically interact and synergistically regulate ciliome gene expression. C. elegans FKH-8 function can be replaced by mouse FOXJ1 and FOXN4 but not by other members of other mouse FKH subfamilies. In conclusion, RFX and FKH TF families act jointly as direct regulators of ciliome genes also in sensory ciliated cell types suggesting that this regulatory logic could be an ancient trait predating functional cilia sub-specialization.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data file 1 and 3 contain all raw data and statistical analysis for figures, Source Data file 2 contains information regarding gene lists and bioinformatics analysis, Source Data file 4 has all the information regarding plasmids, strains and primers.
-
The 1168 Encyclopedia of DNA elements (ENCODE): Data portal update.ENCODE database:ENCFF818YOR, ENCFF549ZSK, ENCFF694MNH, ENCFF552OQU, ENCFF357NSB, ENCFF496CFD, ENCFF092YIJ, ENCFF799WBN, ENCFF810HSZ, ENCFF554KQD, ENCFF390OSN, ENCFF433BEM, ENCFF960EQR, ENCFF792JXA, ENCFF761XWC, ENCFF384GUN, ENCFF803WZH, ENCFF448URK, ENCFF827XAE, ENCFF595SML, ENCFF803QRP, ENCFF587FBJ, ENCFF789TVB, ENCFF816EMR, ENCFF554VDX, ENCFF241SCQ, ENCFF202WJY, ENCFF017FUN, ENCFF798RPP, ENCFF541MIX, ENCFF176UKF, ENCFF947PYR, ENCFF786PUW, ENCFF400VSR, ENCFF786PQH, ENCFF398DRS, ENCFF868IPD, ENCFF409ZRG, ENCFF303QBQ, ENCFF671UBP, ENCFF273RBS, ENCFF995PYF, ENCFF897INS, ENCFF489OMV.
-
scRNAseq L2 stageNCBI Gene Expression Omnibus, GSE126954.
-
scRNAseq L4 stageNCBI Gene Expression Omnibus, GSE136049.
Article and author information
Author details
Rebeca Brocal-Ruiz
Funding
HORIZON EUROPE European Research Council (ERC-2020-COG-101002203(NEUROCODE))
- Rebeca Brocal-Ruiz
- Ainara Esteve-Serrano
- Carlos Mora-Martínez
- Nuria Flames
Ministerio de ciencia e innovacion (BES-2015-072799)
- Rebeca Brocal-Ruiz
Ministerio de ciencia e innovacion (PID2020-115635RB-I00)
- Rebeca Brocal-Ruiz
- Ainara Esteve-Serrano
- Carlos Mora-Martínez
- Nuria Flames
European Research Council (ERC-2011-StG_20101109)
- Rebeca Brocal-Ruiz
- Ainara Esteve-Serrano
- Carlos Mora-Martínez
- Nuria Flames
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Douglas Portman, University of Rochester, United States
Version history
- Preprint posted: September 15, 2021 (view preprint)
- Received: May 26, 2023
- Accepted: July 7, 2023
- Accepted Manuscript published: July 14, 2023 (version 1)
- Version of Record published: August 1, 2023 (version 2)
Copyright
© 2023, Brocal-Ruiz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 855
- views
-
- 143
- downloads
-
- 2
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in C. elegans
eLife 12:e89702.
https://doi.org/10.7554/eLife.89702
Further reading
-
- Chromosomes and Gene Expression
- Developmental Biology
Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, which correlates with polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.
-
- Developmental Biology
Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.
