Biology subjects

Martens, J. R.

Publications and source records attributed to Martens, J. R..

3 recordsLinked to original sources

bioRxiv2023

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

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 of olfactory 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 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 and for development of the OSNs.

neuroscience↗

bioRxiv2019

Inhibitory signaling in mammalian olfactory transduction potentially mediated by Gαo

Olfactory GPCRs (ORs) in mammalian olfactory receptor neurons (ORNs) mediate excitation through the Gs family member Golf. Here we tentatively associate a second G protein, Go, with inhibitory signalling in mammalian olfactory transduction by first showing that odor evoked phosphoinositide 3-kinase (PI3K)-dependent inhibition of signal transduction is absent in the native ORNs of mice carrying a conditional OMP-Cre based knockout of Go. We then identify an OR from native rat ORNs that are activated by octanol through cyclic nucleotide signaling and inhibited by citral in a PI3K-dependent manner. We show that the OR activates cyclic nucleotide signaling and PI3K signaling in a manner that reflects its functionality in native ORNs. Our findings lay the groundwork to explore the interesting possibility that ORs can interact with two different G proteins in a functionally identified, ligand-dependent manner to mediate opponent signaling in mature mammalian ORNs.

neuroscience↗

bioRxiv2018

INPP5E controls ciliary localization of phospholipids and odor response kinetics in a mouse model of Joubert syndrome

Ciliopathies manifested in part by a dysfunction of several phosphoinositide 5phosphatases constitute Lowes, Dent disease 2 and Joubert syndromes through critical involvement of properly functioning primary cilia (PC). We showed that deletion of INPP5E under the control of OMP-Cre in mature mouse olfactory sensory neurons (OSNs) led to a dramatic redistribution of PI(4,5)P2 (PIP2) in cilia, significant reduction of PI(3,4)P2 and enrichment of PI(3,4,5)P3 in knobs. Redistribution of the phospholipids accompanied marked elongation of cilia in INPP5E-OMP knockout (KO) OSNs. Such a dramatic remodeling of phospholipid composition however did not affect other integral membrane lipids (cholesterol, sphingomyelin, glycosylated phosphaditylinositol, phosphatidylserine). Proteins known to bind with high affinity PIP2 entered the cilia of the KO OSNs. Loss of INPP5E did not affect ciliary localization of endogenous olfactory receptor M71/M72 or distribution and movement of IFT122 particles implicating independent of phospholipids mechanism of retrograde protein transport in cilia of mature OSNs. Net odor sensitivity and response magnitude as measured by EOG was not affected by the mutation. However, odor adaptation in the KO mouse was significantly impaired resulting in less efficient recovery and altered inactivation kinetics of the odor response at the EOG and single-cell level. These findings implicate phosphoinositide-dependent regulation of active Ca2+ extrusion in OSNs whereby controlling the rate of sensory adaptation.\n\nSignificance statementCurrently there are little if any available treatment to cure congenital ciliopathies. This is in part due to lack of basic knowledge of cilia biology. Olfactory cilia as well as primary cilia appear to be a phospholipid privileged organelle distinct from the rest of plasma membrane albeit sharing its continuity. We characterized distribution of several critically important for cell biology phospholipids and showed that their balance, especially of PIP2, is disrupted in Joubert syndrome animal model and has functional implications. Virally assisted delivery of wild type INPP5E to the mutant OSNs was able to restore localization of PIP2 and rescued impaired response to odor.

neuroscience↗