Aviles, E. C. | Search bioRxiv

bioRxiv2023

High temporal frequency light response in mouse retina is mediated by ON and OFF bipolar cells and requires FAT3 signaling

Vision is initiated by the reception of light by photoreceptors and subsequent processing via downstream retinal neurons. Proper cellular organization depends on the multi-functional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here we investigated the retinal function of Fat3 mutant mice and found decreases in physiological and perceptual responses to high frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. The role of FAT3 in the response to high temporal frequency flashes depends upon its ability to transduce an intracellular signal. Mechanistically, FAT3 binds to the synaptic protein PTP{sigma}, intracellularly, and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. These findings expand the repertoire of FAT3s functions and reveal its importance in bipolar cells for high frequency light response.

neuroscience↗

bioRxiv2022

Olfactory microvillar tuft cells direct neurogenesis during allergic inflammation

The olfactory neuroepithelium serves as a sensory organ for odors and is part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. A subset of these, microvillous cells (MVCs), are strategically positioned at the apical surface but their specific functions are still enigmatic and their relationship to the rest of the solitary chemosensory cell family is unclear. Here, we establish that the larger family of MVCs comprises tuft cells and ionocytes in both mice and humans. Olfactory TRPM5+ tuft-MVCs share a core transcriptional profile with the chemosensory tuft family, prominently including the machinery for lipid mediator generation. Integrating analysis of the respiratory and olfactory epithelium, we define the unique receptor expression of TRPM5+ tuft-MVC compared to the G[a]-gustducin+ respiratory tuft cells and characterize a new population of glandular DCLK1+ tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we employed an integrated single-cell transcriptional and protein analysis. We defined a remodeling olfactory epithelial switch pathway with induction of Chil4 and a distinct pathway of proliferation of the quiescent olfactory horizontal basal stem cell (HBC), both triggered in the absence of significant olfactory apoptosis. While the Chil4 pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as both sensors for allergens and regulators of olfactory stem cell responses. Together our data provide high resolution characterization of the nasal tuft cell heterogeneity and uncover a novel mechanism by which TRPM5+ tuft cells direct the olfactory mucosal response to allergens. One Sentence SummaryWe identify the enigmatic TRPM5+ olfactory microvillous cells as tuft cells, and show their functional role as regulators of olfactory stem cell proliferation in response to environmental signals.

immunology↗