Foxj1 controls olfactory ciliogenesis and differentiation program of the olfactory sensory neurons

Abstract

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that ofolfactory marker protein(omp) involved in odor-evoked signal transduction. In line with this, response to bile acid, an odor detected by OMP-positive OSNs, was significantly diminished infoxj1mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia and for development of the OSNs.

Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in Caenorhabditis elegans

“…Vertebrate sensory ciliogenesis has been reported to be unaffected in FoxJ1 loss of function mutants ( Choksi et al, 2014 ); thus, FoxJ1 role as a master regulator of ciliogenesis seems restricted to motile ciliary cell types. Interestingly, a recent report indicates that both zebrafish and mouse FoxJ1 mutants display ciliary defects in Olfactory Sensory Neurons, which display an atypical 9+2 sensory cillium ( Rayamajhi et al, 2023 ). In Xenopus , FoxN4 binds similar genomic regions to FoxJ1 and it is also required for motile ciliome gene expression ( Campbell et al, 2016 ).…”

“…In addition, functional paralog substitutions among TFs of the same family have been described to occur in evolution ( Tarashansky et al, 2021 ). Importantly, although FoxJ1 and FoxN4 mutants do not show major ciliome gene expression defects in non-motile ciliated cell types ( Brody et al, 2000 ; Campbell et al, 2016 ; Chen et al, 1998 ; Stubbs et al, 2008 ; Yu et al, 2008 ) a recent report describes ciliary defects in vertebrate Olfactory Sensory Neurons in Foxj1 mutants ( Rayamajhi et al, 2023 ). Other members of FoxJ and FoxN subfamilies are broadly expressed in mouse neurons, which all display primary cilia ( Zeisel et al, 2018 ).…”

The evolutionary conserved choroid plexus sustains the homeostasis of brain ventricles in zebrafish

“…To create the genetic line to label fabp7b-expressing cells specifically, the short homology mediated knockin strategy was used (Rayamajhi et al, 2023;Welker et al, 2021;Wierson et al, 2020) First, a Cas9 target site was selected in exon 4 of fabp7b gene using by CHOPCHOP (http://chopchop.cbu.uib.no/). The sgRNA was synthesized by the cloning-free gRNA in vitro synthesis (Welker et al, 2021;Wierson et al, 2020) and Cas9 mRNA from the pT3TS-nCas9n plasmid (Addgene) with mMESSAGE mMACHINE TM T3 transcription kit (Thermo Fisher Scientific).…”