Journal Article

DZNE-2024-00121

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The forkhead transcription factor Foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation.

Rayamajhi, D. ; Ege, M. ; Ukhanov, K. ; Ringers, C. ; Zhang, Y. ; Jung, I. ; D'Gama, P. P. ; Li, S. S. ; Cosacak, M. I.DZNE* ; Kizil, C.Extern* ; Park, H.-C. ; Yaksi, E. ; Martens, J. R. ; Brody, S. L. ; Jurisch-Yaksi, N. ; Roy, S.

2024
PLoS Lawrence, KS

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Please use a persistent id in citations: doi:10.1371/journal.pbio.3002468

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 traditionally 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 of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acids, odors detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant 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, as well as for the development of the OSNs.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Zebrafish: genetics (MeSH) ; Zebrafish: metabolism (MeSH) ; Cilia: metabolism (MeSH) ; Forkhead Transcription Factors: genetics (MeSH) ; Forkhead Transcription Factors: metabolism (MeSH) ; Olfactory Receptor Neurons (MeSH) ; Olfactory Mucosa (MeSH) ; Forkhead Transcription Factors

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Contributing Institute(s):

1. Mechanisms of Induced Plasticity of the Vertebrate Brain (AG Kizil)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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