TY  - JOUR
AU  - Rayamajhi, Dheeraj
AU  - Ege, Mert
AU  - Ukhanov, Kirill
AU  - Ringers, Christa
AU  - Zhang, Yiliu
AU  - Jung, Inyoung
AU  - D'Gama, Percival P
AU  - Li, Summer Shijia
AU  - Cosacak, Mehmet Ilyas
AU  - Kizil, Caghan
AU  - Park, Hae-Chul
AU  - Yaksi, Emre
AU  - Martens, Jeffrey R
AU  - Brody, Steven L
AU  - Jurisch-Yaksi, Nathalie
AU  - Roy, Sudipto
TI  - The forkhead transcription factor Foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation.
JO  - PLoS biology
VL  - 22
IS  - 1
SN  - 1544-9173
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2024-00121
SP  - e3002468
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Humans
KW  - Mice
KW  - Zebrafish: genetics
KW  - Zebrafish: metabolism
KW  - Cilia: metabolism
KW  - Forkhead Transcription Factors: genetics
KW  - Forkhead Transcription Factors: metabolism
KW  - Olfactory Receptor Neurons
KW  - Olfactory Mucosa
KW  - Forkhead Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38271330
C2  - pmc:PMC10810531
DO  - DOI:10.1371/journal.pbio.3002468
UR  - https://pub.dzne.de/record/267357
ER  -