Biology subjects

Bauer, R.

Publications and source records attributed to Bauer, R..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

ADAM17 regulates hepatic DNA damage repair and tumour formation

BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Still, therapy options for this tumour entity are limited and novel therapeutic options are highly sought after. Genomic instability of hepatocytes promotes oncogenic transformation and underlies the regulation of micro-environmental signalling cues. The membrane-bound a disintegrin and metalloprotease (ADAM) 17 is a major regulator of micro-environmental signals through the proteolytic release of paracrine factors. However, its role in hepatic DNA damage repair and its contribution to hepatic tumourigenesis is still unclear. MethodsWe investigated the effect of ADAM17 on diethylnitrosamine (DEN)-induced acute DNA damage and subsequent DNA damage repair by utilizing mice with ubiquitous or myeloid-specific genetic deficiency in ADAM17. DNA double strand breaks and inflammation were investigated by immunofluorescence of liver tissue sections. tumourigenesis in mice with myeloid-specific ADAM17-deficiency was investigated in a chemically induced hepatocarcinogenesis model. ResultsADAM17 on myeloid cells, in particular Kupffer cells is essentially involved in the non-cell autonomous regulation of DNA damage repair in hepatocytes. Parenchymal ADAM17 regulates hepatocyte fate and recruitment of infiltrating myeloid cells. Furthermore, myeloid ADAM17 promotes hepatic tumour initiation and correlates with poor prognosis in human HCC. ConclusionsWe identified ADAM17, in particular on myeloid cells as an essential driver of hepatic tumourigenesis and as a potential novel drug target for the treatment of hepatic malignancies.

cancer biology↗

bioRxiv2024

The stress of carrying CRISPR-Cas

Streptococcus anginosus (S. anginosus) is a commensal that can cause severe invasive bacterial infections. A considerable percentage of S. anginosus strains harbor CRISPR-Cas systems, which apart from being a bacterial immunity system can play an important role regarding the adaptation to environmental stress. The functionality of S. anginosus CRISPR-Cas systems has previously not been investigated. To address this, we created a set of deletion mutants in the CRISPR-Cas type II-A system of the S. anginosus SK52 type strain, targeting the nuclease Cas9 and the CRISPR array. Testing these strains in a plasmid clearance assay, we were able to confirm CRISPR-Cas activity. Furthermore, the role of the S. anginosus CRISPR-Cas system was investigated under various stress conditions such as UV light, hydrogen peroxide exposure, and high-temperatures in wildtype S. anginosus and CRISPR-Cas mutant strains. Under these conditions, survival was significantly lower in strains carrying cas9. Bacterial growth and metabolic activity in Alamar blue assays was also negatively affected by the presence of cas9 in S. anginosus. In summary we found that the presence of a functional CRISPR-Cas system in S. anginosus leads to measurable metabolic and fitness costs for the wildtype strain. Carrying cas9 was associated with an impaired stress response in our experiments and may thus explain, why many strains of this species lack CRISPR-Cas. Author SummaryThe bacterial immunity system CRIPRS-Cas provides protection against invading foreign genetic material. Despite this obvious advantage only about 50% of bacteria carry CRISPR-Cas. To investigate the CRISPR system of Streptococcus anginosus, which can cause serious bacterial infections and has recently been linked to gastric cancer, we created a set of mutants in different loci of the CRISPR system. Exposing these mutants to stress through UV-light, hydrogen peroxide and high temperatures, we could show that carrying the CRISPR nuclease gene Cas9 is associated with impaired survival under harsh conditions. Strains lacking the nuclease gene had a better growth and higher metabolic activity than the wildtype strain. In summary we found that the presence of a functional CRISPR-Cas system in S. anginosus leads to considerable metabolic and fitness costs. Carrying cas9 was associated with an impaired stress response in our experiments and may thus explain, why many strains of this species lack CRISPR-Cas.

microbiology↗

bioRxiv2023

Printing, Characterising, and Assessing Transparent 3D Printed Lenses for Optical Imaging

High-quality lens production has involved subtractive manufacturing methods for centuries. These methods demand specialist equipment and expertise that often render custom high-grade glass optics inaccessible. We aimed to develop a low-cost, accessible, and reproducible method to manufacture high-quality three-dimensional (3D) printed lenses using consumer-grade technology. Various planoconvex lenses were produced using a consumer-grade 3D printer and low-cost spin coating setup, and printed lenses were compared to commercial glass counterparts. A range of mechanical and optical methods are introduced to determine the surface quality and curvature of 3D printed lenses. Amongst others, high-resolution interference reflection microscopy methods were used to reconstruct the convex surface of printed lenses and quantify their radius of curvature. The optical throughput and performance of 3D printed lenses were assessed using optical transmissivity measurements and classical beam characterisation methods. We determined that 3D printed lenses had comparable curvature and performance to commercial glass lenses. Finally, we demonstrated the application of 3D printed lenses for brightfield transmission microscopy, resolving sub-cellular structures over a 2.3 mm field-of-view. The high reproducibility and comparable performance of 3D printed lenses present great opportunities for additive manufacturing of bespoke optics for low-cost rapid prototyping and improved accessibility to high-quality optics in low-resource settings.

biophysics↗

bioRxiv2023

Low-cost 3D printed lenses for brightfield and fluorescence microscopy

We present the fabrication and implementation of low-cost optical quality 3D printed lenses, and their application as microscope objectives with different prescriptions. The imaging performance of the 3D printed lenses was benchmarked against commercially available optics including a 20 mm focal length 12.7 mm diameter NBK-7 plano-convex lens used as a low magnification objective, and a separate high magnification objective featuring three 6 mm diameter NBK-7 lenses with different positive and negative focal lengths. We describe the design and manufacturing processes to produce high-quality 3D printed lenses. We tested their surface quality using a stylus profilometer, showing that they conform to that of commercial glass counterpart lenses. The 3D printed lenses were used as microscope objectives in both brightfield and epi-fluorescence imaging of specimens including onion, cyanobacteria, and variegated Hosta leaves, demonstrating a sub-cellular resolution performance obtained with low-cost 3D printed optical elements within brightfield and fluorescence microscopy.

biophysics↗

bioRxiv2023

Retinal waves in adaptive rewiring networks orchestrate convergence and divergence in the visual system

Spontaneous retinal wave activity shaping the visual system is a complex neurodevelopmental phenomenon. Retinal ganglion cells are the hubs through which activity diverges throughout the visual system. We consider how these divergent hubs emerge, using an adaptively rewiring neural network model. Adaptive rewiring models show in a principled way how brains could achieve their complex topologies. Modular small-world structures with rich club effects and circuits of convergent-divergent units emerge as networks evolve, driven by their own spontaneous activity. Arbitrary nodes of an initially random model network were designated as retinal ganglion cells. They were intermittently exposed to the retinal waveform, as the network evolved through adaptive rewiring. A significant proportion of these nodes developed into divergent hubs within the characteristic complex network architecture. The proportion depends parametrically on the wave incidence rate. Higher rates increase the likelihood of hub formation, while increasing the potential of ganglion cell death. In addition, direct neigbours of designated ganglion cells differentiate like amacrine cells. The divergence observed in ganglion cells resulted in enhanced convergence downstream, suggesting that retinal waves control the formation of convergence in LGN. We conclude that retinal waves stochastically control the distribution of converging and diverging activity in evolving complex networks.

neuroscience↗

bioRxiv2023

Nucleotide sharing through gap junctions buffers replication stress

Cell proliferation underlying tissue growth and homeostasis, requires high levels of metabolites such as deoxynucleotides (dNTPs). The dNTP pool is known to be tightly cell-autonomously regulated via de novo synthesis and salvage pathways. Here, we reveal that nucleotides can also be provided to cells non-autonomously by surrounding cells within a tissue. Using Drosophila epithelial tissues as models, we find that adult intestinal stem cells are highly sensitive to nucleotide depletion whereas wing progenitor cells are not. Wing progenitor cells share nucleotides through gap junction connections, allowing buffering of replication stress induced by nucleotide pool depletion. Adult intestinal stem cells, however, lack gap junctions and cannot receive dNTPs from neighbors. Collectively, our data suggest that gap junction-dependent sharing between cells can contribute to dNTP pool homeostasis in vivo. We propose that inherent differences in cellular gap junction permeability can influence sensitivity to fluctuations of intracellular dNTP levels. One-Sentence SummaryThe nucleotide pool can be shared between adjacent cells through gap junctions allowing tissue-level buffering of replication stress.

developmental biology↗

bioRxiv2023

NAIP-NLRC4 Inflammasome Activation in Tuft Cells Activates a PGD2-ILC3 Signaling Circuit that Protects Against Enteric Infection.

Intestinal epithelial cells (IEC) use innate sensing pathways to distinguish pathogens from commensals. One such pathway, the NAIP--NLRC4 inflammasome, initiates extrusion of infected IEC and mediator release upon cytosolic bacterial sensing. Tuft cells are primarily known for their function in anti-parasite immunity. We previously reported that activation of the inflammasome in tuft cells leads to release of prostaglandin D2 (PGD2). We test the hypothesis that tuft cell specific release of PGD2 after inflammasome activation initiates antibacterial responses. NAIP--NLRC4 inflammasome activation in tuft cells leads to a type 3 antimicrobial response with increased IL-22 and antimicrobial protein levels within the small intestine, which is dependent on PGD2 signaling. A subset of ILC3 express the PGD2 receptor CRTH2 and we show them as the source of the increased IL-22. Inflammasome activation in tuft cells also leads to better control of Salmonella Typhimurium. These data support that intestinal tuft cells can also induce antibacterial responses. SummaryPGD2 release after NAIP--NLRC4 inflammasome activation in tuft cells signals onto ILC3s and mediates host defense mechanisms against Salmonella Typhimurium within the small intestine. Tuft cells therefore not only promote immune reactions against parasites, but also bacteria.

immunology↗

bioRxiv2023

Proteomic analysis of peripheral nerve myelin during murine aging

Aging of the peripheral nervous system (PNS) is associated with structural and functional changes that lead to a reduction in regenerative capacity and the development of age-related peripheral neuropathy. Myelin is central to maintaining physiological peripheral nerve function and differences in myelin maintenance, degradation, formation and clearance have been suggested to contribute to age-related PNS changes. Recent proteomic studies have elucidated the complex composition of the total myelin proteome in health and its changes in neuropathy models. However, changes in the myelin proteome of peripheral nerves during aging have not been investigated. Here we show that the proteomes of myelin fractions isolated from young and old nerves show only subtle changes. In particular, we found that the three most abundant peripheral myelin proteins (MPZ, MBP and PRX) do not change in old myelin fractions. We also show a tendency for high-abundance myelin proteins other than these three to be downregulated, with only a small number of ribosome-related proteins significantly downregulated and extracellular matrix proteins such as collagens upregulated. In addition, we illustrate that the peripheral nerve myelin proteome reported in this study is suitable for assessing myelin degradation and renewal during peripheral nerve degeneration and regeneration. Our results suggest that the peripheral nerve myelin proteome is relatively stable and undergoes only subtle changes in composition during mouse aging. We proffer the resultant dataset as a resource and starting point for future studies aimed at investigating peripheral nerve myelin during aging. Said datasets are available in the PRIDE archive under the identifier PXD040719 (aging myelin proteome) and PXD041026 (sciatic nerve injury proteome).

neuroscience↗

bioRxiv2023

Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury

Preconditioning with LPS induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are CNS-resident immune cells that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, - using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins Stat1/2.

neuroscience↗

bioRxiv2022

Tocilizumab treatment leads to early resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19

High interleukin (IL)-6 levels are associated with more severe clinical manifestations in patients hospitalized with COVID-19, but the complex role of IL-6 in antiviral and inflammatory processes has made it difficult to decipher its involvement in the disease. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab in addition to identifying novel pharmacodynamic biomarkers. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysregulation associated with severe COVID-19, indicating greater anti-inflammatory activity relative to standard of care and potentially leading to faster recovery in patients hospitalized with COVID-19. One sentence summaryInterleukin-6 receptor blockade with tocilizumab accelerated resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19

immunology↗

bioRxiv2022

Miniaturised structured illumination microscopy using two 3-axis MEMS micromirrors

We present the development and performance characterisation of a novel structured illumination microscope (SIM) in which the grating pattern is generated using two optical beams controlled via 2 micro-electro-mechanical system (MEMS) three-axis scanning micromirrors. The implementation of MEMS micromirrors to accurately and repeatably control angular, radial and phase positioning delivers flexible control of the fluorescence excitation illumination, with achromatic beam delivery through the same optical path, reduced spatial footprint and cost-efficient integration being further benefits. Our SIM architecture enables the direct implementation of multi-colour imaging in a compact and adaptable package. The two-dimensional SIM system approach is enabled by a pair of 2 mm aperture electrostatically actuated three-axis micromirrors having static angular tilt motion along the x- and y- axes and static piston motion along the z-axis. This allows precise angular, radial and phase positioning of two optical beams, generating a fully controllable spatial interference pattern at the focal plane by adjusting the positions of the beam in the back-aperture of a microscope objective. This MEMS-SIM system was applied to fluorescent bead samples and cell specimens, and was able to obtain a variable lateral resolution improvement between 1.3 and 1.8 times the diffraction limited resolution.

cell biology↗

bioRxiv2021

Salmonella Typhimurium induces NAIP/NLRC4- and NLRP3/ASC-independent, caspase-1/4-dependent inflammasome activation in human intestinal epithelial cells

Salmonella enterica serovar Typhimurium is a gram-negative pathogen that causes diseases ranging from gastroenteritis to systemic infection and sepsis. Salmonella uses type III secretion systems (T3SSs) to inject effectors into host cells. While these effectors are necessary for bacterial invasion and intracellular survival, intracellular delivery of T3SS products also enables detection of Salmonella by cytosolic immune sensors. Upon detecting translocated Salmonella ligands, these sensors form multimeric complexes called inflammasomes, which activate caspases that lead to proinflammatory cytokine release and pyroptosis. In particular, the Salmonella T3SS needle, inner rod, and flagellin proteins activate the NAIP/NLRC4 inflammasome in murine intestinal epithelial cells (IECs), which leads to restriction of bacterial replication and extrusion of infected IECs into the intestinal lumen, thereby preventing systemic dissemination of Salmonella. While these processes are studied quite well in mice, the role of the NAIP/NLRC4 inflammasome in human IECs remains unknown. Unexpectedly, we found the NAIP/NLRC4 inflammasome is dispensable for early inflammasome responses to Salmonella in both human intestinal epithelial cell lines and organoids. Additionally, the NLRP3 inflammasome and the adaptor protein ASC are not required for inflammasome activation in Caco-2 cells. Instead, we observed a partial requirement for caspase-1, and a necessity for caspase-4 and GSDMD pore-forming activity in mediating inflammasome responses to Salmonella in Caco-2 cells. These findings suggest that unlike murine IECs, human IECs do not rely on NAIP/NLRC4, and also do not use NLRP3/ASC. Instead, they primarily use caspases-1 and -4 to mediate early inflammasome responses to SPI-1-expressing Salmonella.

microbiology↗

bioRxiv2021

Retinal self-organization: a model of RGC and SAC mosaic formation

Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. These mosaics enable uniform sampling of visual information and are formed to varying degrees across cell types. Retinal ganglion cells (RGC) and amacrine cells (including starburst amacrine cells (SAC)) are notably known to exhibit such layouts. Mechanisms responsible for the formation of such organised structures and their requirements are still not well understood. Mosaic formation follows three main principles: (1) homotypic cells prevent nearby cells from adopting the same type, (2) cell tangential migration, with homotypic cell repulsion, (3) cell death (with RGCs exhibiting high rates of apoptosis). Here, we use BioDynaMo, an agent-based simulation framework, to build a detailed and mechanistic model of mosaic formation. In particular, we investigate the implications of the three theories for RGCs mosaic formation. We report that the cell migration mechanism yields the most regular mosaics and that cell death can create regular mosaics only if the death rate is kept below 30%, after which cell death has a negative impact on mosaic regularity. In addition, and in accordance with recent studies, we propose here that low density RGC type mosaics exhibit on average low regularities, and thus we question the relevance of regular spacing as a criterion for a group of RGCs to form a RGC type. We also investigate SAC mosaics formation and possible interactions between the ganglion cell layer (GCL) and inner nuclear layer (INL) populations. Investigations are conducted both experimentally and by applying our simulation model to the SAC population. We report that homotypic interactions between the GCL and INL populations during mosaics creation are required to reproduce the observed SAC mosaics characteristics. This suggests that the GCL and INL populations of SACs might not be independent during retinal development. Author SummaryRetinal function depends on cells self-organisation during early development. Understanding the mechanisms underlying this self-organisation could improve not only our comprehension of the retina and its development but also of the cortex. Ultimately, this could lead to novel therapeutic approaches for developmental diseases. Computational models can be of precious help to study this process of self-organisation, given that they are biologically plausible. In this sense, it is important that implemented developmental mechanisms follow the principle of locally available information, without any global knowledge or external supervisor. Here, we follow this principle to investigate mosaic formation during retinal development. In this work, we demonstrate that tangential migration is the only mechanism able to form regular mosaics and that the GCL/INL SAC populations might not be independent during their mosaic formation. More, we question the relevance of regular spacing for RGC types classification.

bioinformatics↗

bioRxiv2021

Angicin, a novel bacteriocin of Streptococcus anginosus

As a conserved defense mechanism, many bacteria produce antimicrobial peptides, called bacteriocins, which give a colonization advantage in a multispecies environment. Here the first bacteriocin of Streptococcus anginosus, designated Angicin, is described. S. anginosus is commonly described as a commensal, however it also possesses a high pathogenic potential. Therefore, understanding factors contributing to its host colonization and persistence are important. A radial diffusion assay was used to identify S. anginosus BSU 1211 as a potent bacteriocin producer. By genetic mutagenesis the background of bacteriocin production and the bacteriocin gene itself were identified. Synthetic Angicin shows high activity against closely related streptococci, listeria and vancomycin resistant enterococci. It has a fast mechanism of action and causes a membrane disruption in target cells. Angicin, present in cell free supernatant, is insensitive to changes in temperature from -70 to 90 {degrees}C and pH values from 2-10, suggesting that it represents an interesting compound for potential applications in food preservation or clinical settings.

microbiology↗

bioRxiv2021

The HDL particle composition determines its anti-tumor activity in pancreatic cancer

Despite significant efforts in the last years to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Late diagnosis and a complex, fibrotic tumor microenvironment produces a therapeutically hardly approachable situation with rapidly emerging resistance mechanisms. In response to this hostile microenvironment, previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis was shown to promote a growth advantage to, and chemotherapy resistance for PDAC tumor cells. Here, we demonstrate that efficient, net-cholesterol removal from cancer cells, driven by high-density lipoprotein (HDL) mediated efflux, results in a significant PDAC cell growth reduction, apoptosis and a decreased PDAC tumor development in vivo. This effect is driven by an HDL particle composition-dependent interaction with SR-B1 and ABCA1 on cancer cells, two major lipid flux receptors, which differentially regulate cholesterol transport at the plasma membrane. Eventually, we show that pancreatic cancer patients display reduced plasma levels of HDL-cholesterol, directly translating into a reduced cholesterol efflux capacity of patient-derived plasma samples. We conclude that cholesterol depletion from PDAC cells, together with possible interventions that shunt the import and endogenous synthesis pathways of cholesterol, might represent a promising strategy to increase and complement the currently available treatment options to improve the prognosis of patients suffering from PDAC.

cancer biology↗

bioRxiv2021

The NLRP3/eIF2 axis drives cell cycle progression in acute myeloid leukemia

Aberrant activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates numerous inflammatory diseases. Oncogenes can activate the NLRP3 inflammasome and thereby promote myeloproliferative neoplasia, suggesting a crucial role of NLRP3 in the malignant transformation of hematopoietic cells. Here, we show that bone marrow-derived mononuclear cells of AML patients display enhanced expression of NLRP3, IL-1{beta} and IL-18 and that high-level expression of NLRP3 is linked to poor survival of AML patients. Pharmacological and genetic inhibition of NLRP3 inflammasome activation attenuated cell proliferation of MOLM-13 AML cells in vitro. In vivo, genetic inhibition of NLRP3 in MOLM-13 AML cells resulted in reduced engraftment potential in xenografts, along with reduced splenomegaly and organ infiltration. Differential proteomic analysis revealed the eIF2 pathway as potential target of NLRP3 in AML, with a significant increase of eIF2 phosphorylation upon NLRP3 inhibition. NLRP3 inhibition also caused a strong decrease in cyclin - dependent kinases CDK4 and CDK6, accompanied by an upregulation of the CDK inhibitor p21 (CDKN1A) and a marked arrest of cell cycle progression in the G0/G1 phase, consistent with the role of eIF2 phosphorylation as negative cell cycle regulator. Taken together, we show that inhibition of the NLRP3 inflammasome reduces AML cell proliferation by promoting eIF2 phosphorylation, which in turn enhances the expression of cell cycle arrest genes such as p21. Thus, the study uncovers the NLRP3/eIF2 axis as new driver of AML proliferation and proposes a novel therapeutic treatment of AML by targeted inhibition of NLRP3 activation.

immunology↗

bioRxiv2021

Tuneable wide-field illumination and single-molecule photoswitching with a single MEMS mirror

Homogeneous illumination in single-molecule localization microscopy (SMLM) is key for the quantitative analysis of super-resolution images. Therefore, different approaches for flat-field illumination have been introduced as alternative to the conventional Gaussian illumination. Here, we introduce a single microelectromechanical systems (MEMS) mirror as a tuneable and cost-effective device for adapting wide-field illumination in SMLM. In flat-field mode the MEMS allowed for consistent SMLM metrics across the entire field of view. Employing single-molecule photoswitching, we developed a simple yet powerful routine to benchmark different illumination schemes on the basis of local emitter brightness and ON-state lifetime. Moreover, we propose that tuning the MEMS beyond optimal flat-field conditions enables to study the kinetics of photoswitchable fluorophores within a single acquisition.

biophysics↗

bioRxiv2021

Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans

Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have twelve isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive GFP expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.

genetics↗