Polarity Signaling Research Articles

SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation.

SLMAP3 is a constituent of the centrosome and is known to assemble with the striatin-interacting phosphatase and kinase (STRIPAK) complex, where it has been reported to repress Hippo signalling. The global knockout of SLMAP3 in mice results in embryonic/perinatal lethality and stunted growth without changes in the phosphorylation status of YAP. Diverse phenotypes present in the SLMAP3-/- embryos include reduced body axis, small and abnormal organs resembling defects in planar cell polarity (PCP) signalling, while also displaying the notable polycystic kidneys, a known manifestation of ciliopathies. Analysis of cell polarity in primary mouse embryonic fibroblasts (MEFs) including cell migration, orientation and mitotic spindle angle did not reveal any changes due to SLMAP3 loss in these cells, although the expression of DVL3 was significantly reduced. Furthermore, MEFs lacking FGFR1OP2 or STRN3, two other STRIPAK members, did not reveal any significant changes in any of these parameters either. Significant changes in the number of ciliated cells and primary cilium length in SLMAP3 and FGFR1OP2 deficient MEFs were evident, while a reduced primary cilium length was notable in chondrocytes of SLMAP3 deficient embryos. Our findings suggest that SLMAP3 is essential for mouse embryogenesis through novel mechanisms involving the primary cilium/PCP and protein stability independent of Hippo signalling.

Linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse neural tube development.

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be genetically epistatic to Gpr161 with respect to regulation of Shh signaling in mouse neural tube development. The Fuz protein biochemically interacts with Gpr161, and Fuz regulates Gpr161-mediated ciliary localization, a process that might utilize β-arrestin 2. Our study characterizes a previously unappreciated Gpr161-Fuz axis that regulates Shh signaling during mouse neural tube development.

Significant influence of winter Pacific-North American pattern on spring vegetation in mid-high latitude Asia

Abstract Given that the vegetation over mid-high latitude Asia (MHA) has been more variable in recent years, it is necessary to better understand the physical causes of vegetation variations in this region. Based on the normalized difference vegetation index (NDVI), this study reveals a close linkage of the variability of spring (April–May) vegetation in MHA to the winter (December–January–February) Pacific-North American (PNA) pattern. When the winter PNA pattern lies in the positive phase, the NDVI tends to decrease in most parts of the MHA region during the following spring. Further analysis suggests that the lagged influence of winter PNA on spring atmospheric circulations and hence the vegetation in MHA is accomplished by the stratospheric pathway. The positive PNA phase can enhance the upward transport of wave energy into the stratosphere over the high latitudes in winter through the linear constructive interference of zonal wavenumber 1 (WN1), consequently leading to a weaker polar vortex in the stratosphere during February-March. Subsequently, the weakened polar vortex signal propagates downward from the stratosphere to the troposphere, inducing the negative Arctic Oscillation-like circulation with an anomalous cyclonic circulation dominating the MHA region in spring. The anomalous cyclonic circulation further cools the surface air temperature in MHA via modulating downward solar radiation and temperature advection, resulting in a decrease of spring NDVI in situ.

Advances in Plant Auxin Biology: Synthesis, Metabolism, Signaling, Interaction with Other Hormones, and Roles under Abiotic Stress.

Auxin is a key hormone that regulates plant growth and development, including plant shape and sensitivity to environmental changes. Auxin is biosynthesized and metabolized via many parallel pathways, and it is sensed and transduced by both normal and atypical pathways. The production, catabolism, and signal transduction pathways of auxin primarily govern its role in plant growth and development, and in the response to stress. Recent research has discovered that auxin not only responds to intrinsic developmental signals, but also mediates various environmental signals (e.g., drought, heavy metals, and temperature stresses) and interacts with hormones such as cytokinin, abscisic acid, gibberellin, and ethylene, all of which are involved in the regulation of plant growth and development, as well as the maintenance of homeostatic equilibrium in plant cells. In this review, we discuss the latest research on auxin types, biosynthesis and metabolism, polar transport, signaling pathways, and interactions with other hormones. We also summarize the important role of auxin in plants under abiotic stresses. These discussions provide new perspectives to understand the molecular mechanisms of auxin's functions in plant development.

Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling.

Intercellular signaling mediated by evolutionarily conserved planar cell polarity (PCP) proteins aligns cell polarity along the tissue plane and drives polarized cell behaviors during tissue morphogenesis. Accumulating evidence indicates that the vertebrate PCP pathway is regulated by noncanonical, β-catenin-independent Wnt signaling; however, the signaling components and mechanisms are incompletely understood. In the mouse hearing organ, both PCP and noncanonical Wnt (ncWnt) signaling are required in the developing auditory sensory epithelium to control cochlear duct elongation and planar polarity of resident sensory hair cells (HCs), including the shape and orientation of the stereociliary hair bundle essential for sound detection. We have recently discovered a Wnt/G-protein/PI3K pathway that coordinates HC planar polarity and intercellular PCP signaling. Here, we identify Wnt7b as a ncWnt ligand acting in concert with Wnt5a to promote tissue elongation in diverse developmental processes. In the cochlea, Wnt5a and Wnt7b are redundantly required for cochlear duct coiling and elongation, HC planar polarity, and asymmetric localization of core PCP proteins Fzd6 and Dvl2. Mechanistically, Wnt5a/Wnt7b-mediated ncWnt signaling promotes membrane recruitment of Daple, a nonreceptor guanine nucleotide exchange factor for Gαi, and activates PI3K/AKT and ERK signaling, which promote asymmetric Fzd6 localization. Thus, ncWnt and PCP signaling pathways have distinct mutant phenotypes and signaling components, suggesting that they act as separate, parallel pathways with nonoverlapping functions in cochlear morphogenesis. NcWnt signaling drives tissue elongation and reinforces intercellular PCP signaling by regulating the trafficking of PCP-specific Frizzled receptors.

Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation

BackgroundBetel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive.MethodsImmunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE.ResultsWe reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters.ConclusionOur study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.

The nonphototrophic hypocotyl 3 (NPH3) domain protein NRL5 is a trafficking-associated GTPase essential for drought resistance.

The mechanisms of plant drought resistance are unclear but may involve membrane trafficking and metabolic reprogramming, including proline accumulation. Forward genetic screening using a proline dehydrogenase 1 (ProDH1) promoter:reporter identified a drought hypersensitive mutant with a single-amino acid substitution (P335L) in the nonphototrophic hypocotyl 3 (NPH3) domain of NPH3/root phototropism 2-like 5 (NRL5)/naked pins in Yucca 8 (NPY8). Further experiments found that NRL5 and other NPH3 domain proteins are guanosine triphosphatases (GTPases). NRL5, but not NRL5P335L, interacted with the RABE1c and RABH1b GTPases and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) Vesicle-Associated Membrane Protein (VAMP)721/722. These proteins controlled NRL5 localization and connection to trafficking while also being genetically downstream of, and potentially regulated by, NRL5. These data demonstrate that NRL5-mediated restraint of proline catabolism is required for drought resistance and also reveal unexpected functions of the NPH3 domain such that the role of NPH3 domain proteins in signaling, trafficking, and cellular polarity can be critically reevaluated.

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN’ enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.Graphical

Walnut peptide ameliorates DSS-induced colitis in mice by inhibiting inflammation and modulating gut microbiota

The incidence of ulcerative colitis (UC) is increasing each year, and its course is characterized by alternating remission-relapse; currently, there is no effective treatment for UC. Peptides produced from the hydrolysis of walnut proteins have physiological functions such as anti-inflammatory and antioxidant properties. The aim of this study was to analyze the preventive effect of walnut polypeptide (WP) on UC and to preliminarily screen bioactive peptides in WP. The results of in vitro experiments showed that WP was able to alleviate the LPS-induced inflammatory response by inhibiting M1 polarization in Raw 264.7 cells and thereby alleviating the LPS-induced inflammatory response. The results of in vivo experiments showed that dietary supplementation with 500 mg/kg WP significantly alleviated dextran sodium sulfate (DSS)-induced weight loss, colon shortening, and elevated DAI scores. WP treatment was able to suppress DSS-induced inflammatory responses in mice by inhibiting macrophage M1 polarization and NF-κB signaling pathway. WP intervention also helped maintain intestinal barrier integrity by promoting tight junction protein expression and mucus secretion. In addition, 16S rDNA sequencing showed that WP ameliorated gut microbial disorder induced by DSS, as evidenced by a decrease in the abundance of harmful bacteria (Erysipelatoclostridium, Helicobacter, and Parasutterella) and an increase in the abundance of beneficial bacteria (Flavonifractor, Anaerotignum, and Alistipes) after WP intervention. In conclusion, this study demonstrates that WP ameliorates DSS-induced colonic inflammation in mice by inhibiting inflammation, modulating the gut microbiota and repairing the intestinal barrier.

Antenna-waveguide devices with a single horn for satellite communication antenna systems

A technical and recommendations for their use in the development and practical implementation of devices as part of antenna-waveguide paths with a single horn are presented to increase efficiency in monitoring MPA satellite communication systems. The practical implementation of multi-band AVP for MPA is shown. Technical solutions for the construction of multi-band AVP for MPA satellite communication systems and remote sensing complexes, which differ from the known ones by the possibility of expanding the functionality of the AVT. Implementation of the monopulse auto-tracking mode using the H21 mode in dual-band auto-tracking machines using signals of specified polarizations in the required frequency ranges. When receiving signals of orthogonal linear and circular polarizations, the number of combined ranges increases to four.

Band Alignment Modulated Polarity-Switchable PEC Ratiometric Sensor through Coupling a pH-Responsive CuTCPP MOF with i-Motif Sensing tool.

In conventional ratiometric photoelectrochemical (PEC) sensors, the detection and reference signals are output sequentially from two independent photosensitive materials. In such a "two-to-two" ratiometric mode, unavoidable difference during dual-interface modification exists, resulting in questionable ratiometric signals and detection results. To address this issue, we propose a novel "one-to-two" ratiometric PEC sensor on a single electrode interface through pH-modulated band alignment engineering. The double ratiometric signals are generated by the synergistic action of a pH-responsive CuTCPP/WS2 photoelectric substrate material and the i-motif sensing tool. Specifically, a ternary heterostructure to generate a photoanodic detection signal is formed under alkaline conditions between CuTCPP/WS2 and signal label CdS QDs binding to the i-motif. While under acidic conditions, a photocurrent polarity conversion and signaling labels detachment, induced by the band realignment of CuTCPP/WS2 and the i-motif conformational switching, produce a reliable internal reference photocathodic signal. The feasibility of this two-wing signal generation strategy is validated by detecting mycotoxin ochratoxin A, which achieves accurate and reliable ratio detection results. Overall, this work provides guidance for the design of a PEC ratiometric determination system and exhibits great potential to be applied in practical analysis research.

Angiotensin II Type 2 Receptor Inhibits M1 Polarization and Apoptosis of Alveolar Macrophage and Protects Against Mechanical Ventilation-Induced Lung Injury.

Angiotensin II (Ang II) is associated with macrophage polarization and apoptosis, but the role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. However, the effect of AT2Rs on alveolar macrophages and mechanical ventilation-induced lung injury has not been determined.Mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats and LPS-stimulated rat alveolar macrophages (NR8383) were used to determine the effects of AT2Rs, selective AT2R agonists and selective AT1Rs or AT2R antagonists. Macrophage polarization, apoptosis, and related signaling pathways were assessed via western blotting, QPCR and flow cytometry.AT2R expression was decreased in LPS-stimulated rat alveolar macrophages (NR8383). Administration of the AT2R agonist CGP-42112 was associated with an increase in AT2R expression and M2 polarization, but no effect was observed upon administration of the AT2R antagonist PD123319 or the AT1R antagonist valsartan. In mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats, the administration of the AT2R agonist C21 was associated with attenuation of the pathological damage score, lung wet/dry weight, cell count and protein content in BALF. C21 can significantly reduce proinflammatory factor TNF-α, IL-1β levels, increase anti-inflammatory factor IL-4, IL-10 levels in BALF, compared with the model group (p < 0.01). Similarly, compared with those at the same time points, the M1/M2 ratios in alveolar macrophages and apoptosis in peritoneal macrophages at 4h, 6h and 8h in the mechanical ventilation models were lower after C21 administration.These findings indicated that the expression of AT2Rs in alveolar macrophages mediates M1 macrophage polarization and apoptosis and that AT2Rs play a protective role in mediating mechanical ventilation-induced lung injury.

Insights into modifiers effects in differential mobility spectrometry: A data science approach for metabolomics and peptidomics.

Utilizing a data-driven approach, this study investigates modifier effects on compensation voltage in differential mobility spectrometry-mass spectrometry (DMS-MS) for metabolites and peptides. Our analysis uncovers specific factors causing signal suppression in small molecules and pinpoints both signal suppression mechanisms and the analytes involved. In peptides, machine learning models discern a relationship between molecular weight, topological polar surface area, peptide charge, and proton transfer-induced signal suppression. The models exhibit robust performance, offering valuable insights for the application of DMS to metabolites and tryptic peptides analysis by DMS-MS.

Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Planar Cell Polarity Signaling: Coordinated Crosstalk for Cell Orientation.

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior-posterior to left-right embryonic plane polarity through the polarization of cilia in the Kupffer's vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP.

RHO OF PLANTS signalling and the activating ROP GUANINE NUCLEOTIDE EXCHANGE FACTORS: specificity in cellular signal transduction in plants.

Every cell constantly receives signals from its neighbours or the environment. In plants, most signals are perceived by RECEPTOR-LIKE KINASEs (RLKs) and then transmitted into the cell. The molecular switches RHO OF PLANTS (ROP) are critical proteins for polar signal transduction and regulate multiple cell polarity processes downstream of RLKs. Many ROP-regulating proteins and scaffold proteins of the ROP complex are known. However, the spatiotemporal ROP signalling complex composition is not yet understood. Moreover, how specificity is achieved in different ROP signalling pathways within one cell still needs to be determined. This review gives an overview of recent advances in ROP signalling and how specificity by downstream scaffold proteins can be achieved. The composition of the ROP signalling complexes is discussed, focusing on the possibility of the simultaneous presence of ROP activators and inactivators within the same complex to balance ROP activity. Furthermore, this review highlights the function of plant-specific ROP GUANINE NUCLEOTIDE EXCHANGE FACTORS polarizing ROP signalling and defining the specificity of the initiated ROP signalling pathway.

The remnant of the midbody as a cellular signaling mechanism

Cell signaling mechanisms are the basis for intercellular integration and regulation of proliferation and differentiation processes at the systemic level. One of the most plausible ways to control cell-to-cell interaction and targeted distribution of genetic information is for cells to use their own structures that are formed during mitosis and carry RNA-dependent signaling molecules that affect the mechanisms of control of intercellular interaction, cell proliferation and differentiation. The midbody remnant is a microtubule-rich structure that forms between dividing cells in the last stages of cytokinesis. Previously, it was thought to be only a temporary structure of the intercellular bridge during cytokinesis, which served to connect two future daughter cells. This structure is a key regulator of abscission and functions as a signaling platform that coordinates the cytoskeleton and endosomal dynamics during the terminal stages of cell division. The midbody is a subcellular structure that is formed during cell division, during penetration into the cleavage sulcus, when the microtubules of the central spindle are compacted and cross-linked by a thin intracellular bridge connecting the two daughter cells. The midbody plays a key role in organizing cytokinesis by recruiting a variety of mitotic kinases such as Aurora B and Plk1, as well as sulcus endosomes containing Rab11/FIP3, the membrane-rupturing ESCRT complex and the microtubule-rupturing enzyme spastin, all of which are responsible for mediated rupture during the later stages of cytokinesis. The midbodies can serve as extracellular and intracellular polarity signals during early embryogenesis, as well as during epithelialization and polarization of neurons. The molecular mechanism that governs the positioning of the middle body and how it transmits signals to neurons during differentiation or epithelium remains unknown. Importantly, the remains of the middle bodies can also function as intracellular signaling scaffolds that regulate proliferation and fate postmitotic cells. Since these structures can be released outside cells and taken up by other non-mitotic cells, it is suggested that they may function as vehicles for alternative transmission of complex sets of signaling molecules and/or receptors between cells, thus profoundly affecting signaling in general.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Planar Cell Polarity in the Multiciliated Epithelial Lining of the Mouse Eustachian Tube.

Planar cell polarity (PCP) signaling, essential for uniform alignment and directional beating of motile cilia, has been investigated in multiciliated epithelia. As a complex structure connecting the middle ear to the nasopharynx, the eustachian tube (ET) is important in the onset of ear-nose-throat diseases. However, PCP signaling, including the orientation that is important for ciliary motility and clearance function in the ET, has not been studied. We evaluated PCP in the ET epithelium. Morphometric examination of the mouse ET. We performed electron microscopy to assess ciliary polarity in the mouse ET, along with immunohistochemical analysis of PCP protein localization in the ET epithelium. We discovered PCP in the ET epithelium. Motile cilia were aligned in the same direction in individual and neighboring cells; this alignment manifested as ciliary polarity in multiciliated cells. Additionally, PCP proteins were asymmetrically localized between adjacent cells in the plane of the ET. The multiciliated ET epithelium exhibits polarization, suggesting novel structural features that may be critical for ET function. NA Laryngoscope, 134:3795-3801, 2024.