Docosahexaenoic acid (DHA), the predominant n-3 polyunsaturated fatty acid (PUFA) in the brain, promotes neuronal differentiation, neurite outgrowth, and synapse formation. However, the subcellular mechanisms underlying these effects remain unclear. The primary cilium functions as a signaling antenna, with its length influencing signaling capacity; however, the physiological factors regulating cilium length in neurons are largely unknown. This study investigated whether DHA promotes primary cilium elongation in neurons and examined the underlying signaling pathways.

The primary cilium (plural 'cilia') is a highly specialized organelle found on nearly every vertebrate cell. It functions as a sensor, cell cycle regulator and coordinator of multiple signalling transduction pathways. In cholangiocytes, primary cilia extend from the cell surface into the bile duct lumen, acting as chemosensors, mechanosensors and osmosensors in response to changes in bile composition and flow. This primary-cilium-mediated sensing regulates the biliary microenvironment and is crucial to maintaining homeostasis and promoting biliary regeneration. Moreover, alterations in the structure or function of cholangiocyte primary cilia lead to a group of disorders known as biliary ciliopathies, which manifest with a broad range of clinical features including cystic lesions, fibrosis and biliary strictures. This Review aims to provide an overview of the structure and function of cholangiocyte primary cilia and to summarize the known biliary ciliopathies. As most of these diseases currently lack effective treatments targeting their underlying mechanisms, an understanding of this organelle can help to pave the way for novel cilium-targeted therapies.

Pathogenic, presumed gain-of-function variants in the gene KCNT1, which encodes a sodium-activated potassium channel, cause a severe neurodevelopmental disorder with intractable epilepsy. In addition to seizures, affected individuals commonly present with severe respiratory issues and structural heart defects not commonly observed in other genetic pediatric epilepsies, suggesting additional developmental functions for KCNT1 in organs beyond the brain. Here we characterized the spectrum of clinical diagnoses present in a cohort of 46 individuals with genetic variants in KCNT1, ranging from 0 to 19 years of age, by medical record review. We documented the prevalence of diagnoses across organ systems, including dependence on assisted breathing, congenital structural heart defects, urinary dysfunction, and spine deformities, among others. Next, we explored the embryonic expression and function of KCNT1 in diploid frogs (Xenopus tropicalis) and observed expression in developing ciliated tissues such as the brain, heart, kidney, and epidermis. Embryonic perturbation of KCNT1 disrupted developmental signaling pathways and caused ciliogenesis defects in the mucociliary epidermis, a common model for the human airway. Loss of KCNT1 disrupted development of multiciliated cells, reminiscent of recent work on the ion channel Piezo1. Consistently, pharmacological inhibition of Piezo signaling enhanced the ciliogenesis phenotype observed following KCNT1 inhibition, while activation of Piezo1 activity partially rescued ciliogenesis in the context of KCNT1 inhibition. Finally, KCNT1 loss reduced expression of foxj1, a key transcriptional regulator of multiciliated cell specification, linking KCNT1 activity to the transcriptional programs underlying multiciliated cell formation and specification. Together, this work establishes that KCNT1 has embryonic functions in Xenopus beyond regulating neuronal activity, specifically in multiciliated cell development, and identifies an interaction with pharmacologically-tractable Piezo channels that may be productive for therapeutic efforts aimed at inhibiting KCNT1 activity.

Despite a likely role in setting stress tolerance limits, food ration has received limited attention as an ecological factor affecting the cellular stress response (CSR). To study the interactive effects of food and temperature on the proteomic heat shock response, we acclimated intertidal mussels (Mytilus californianus) to four combinations of nearshore (low) and aquaculture (high) phytoplankton levels, combined with low (20 °C) and high (30 °C) aerial temperatures during daytime low tides. Mussels were then exposed to an acute (6 h), aerial heat stress (33 °C) and allowed to recover for 1 h and 25 h in pre-exposure conditions. Proteomic changes in the gill before and after heat shock were measured using label-free liquid-chromatography-mass spectrometry. Compared to other acclimation treatments, low-food-low-temperature (LTLF) mussels modified more splicing factors, heterogeneous nuclear ribonucleoproteins, ribosomal proteins, and translation initiation and elongation factors, suggesting systemic changes to RNA processing, selection, and translation. LTLF mussels also increased chaperones of the actin- and microtubule-associated cytoskeleton and proteins that mature along the endoplasmic reticulum to Golgi secretory pathway. Simultaneously, actin stress fiber formation at focal adhesions and the extracellular matrix, along with anchoring of microtubule-associated cilia, indicate a possible system-wide mechanical breakdown of the cytoskeleton. Signaling proteins causing cytoskeletal changes varied mainly in LTLF mussels and suggest a food-dependent role for prostaglandin synthesis. Overall, the acclimation-dependent proteomic changes show how thermal conditioning and food ration together will shape the CSR of mussels during heat waves.

Several animal groups produce two morphologically distinct types of sperm in the testis, including fertilizing eusperm and non-fertilizing parasperm. This phenomenon, termed sperm dimorphism, is considered to play a role in reproductive strategies such as sperm competition. In the marine gastropod Conomurex luhuanus, parasperm possess numerous globular bodies and the cilia-based undulating membranes. However, the function of the globular bodies and the motility of the undulating membranes remain unclear. Here, we describe the process and regulation of globular body exocytosis in parasperm. Upon dilution in artificial seawater, exocytosis occurs via membrane fusion between globular body membrane and the plasma membrane, followed by the release of globular body contents. Exocytosis was markedly suppressed under Ca2+ -deficient conditions but was enhanced by increases in intracellular Ca2+ induced by an ionophore A23187. In contrast, both the absence of extracellular K[+] and high extracellular K[+] concentrations enhanced exocytosis. On the other hand, the direction of wave propagation of the undulating membrane was reversed by high extracellular Ca2+ concentrations or by treatment with A23187, whereas it was suppressed under high extracellular K[+] conditions. Together, these findings indicate that globular body exocytosis and changes in swimming direction are regulated by different mechanisms. This study provides novel insight into the post-ejaculatory behavior and potential function of parasperm within the female reproductive tract of gastropods.

Pathogens associated with managed bees are frequently detected in wild arthropods, raising concerns about potential negative impacts on biodiversity and fueling scientific, societal, and political debate. However, major gaps remain in our understanding of the mechanisms driving pathogen spillovers, their impacts on recipient hosts, and mitigation strategies. We propose an integrative, holistic research framework beyond the current focus on pathogen detection that centers on the impacts of shared pathogens and on management strategies to mitigate risks. This reframing will help guide future research design and interpretation beyond precautionary principles, advance our understanding of epidemiological risks, and support evidence-based policymaking that balances food security with biodiversity conservation.

Ankyrin Repeat and Sterile Alpha Motif Domain Containing 1A (ANKS1A), also known as ODIN, is a multifunctional adaptor/scaffolding protein that regulates receptor tyrosine kinase signaling and intracellular protein trafficking. While morpholino (MO)-mediated knockdown of Anks1a in Xenopus has been shown to impair ciliogenesis and motile cilia function, its role in early embryonic morphogenesis remains largely unknown. Here we report morphological phenotype images and quantification from morpholino-mediated Anks1a knockdown and mRNA rescue experiments in Xenopus laevis tadpoles. The data document dose-dependent defects in head size, melanocyte distribution, reduced or malformed cardiac region, and gut coiling, together with partial phenotypic rescue upon co-injection of mouse ANKS1A-VN mRNA. After Xenopus anks1a morpholino (xanks1a-MO), 77.6% of embryos were Severe (n = 85); co-injection with mouse ANKS1A-VN mRNA gave 16% Normal, 66% Mild and 18% Severe (n = 100). Raw image files and scoring data are available in the Zenodo repository (DOI: 10.5281/zenodo.21912238).

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, affecting approximately 250 million individuals. Mechanical imbalance serves as both its primary driving force and pathological hallmark. Mechanobiology-based interventions remain constrained by an insufficient understanding of how chondrocytes perceive and adapt to aberrant mechanical environments. Here, we review the cascading mechanisms linking mechanical imbalance to cellular dysfunction in OA and emerging therapeutic strategies targeting these mechanobiological processes. At the biomechanical level, joint mechanical imbalance encompasses both abnormal exogenous loading (trauma, obesity, joint deformity) and alterations in extracellular and pericellular matrix properties, with spatial heterogeneity and temporal dynamics throughout disease progression. At the cellular level, chondrocytes perceive mechanical signals through primary mechanosensors, including mechanosensitive ion channels (Piezo1/2, TRPV4), integrin-focal adhesion complexes, and primary cilia. These signals initiate Ca[2+] signaling and cytoskeletal remodeling and converge on signaling and transcriptional regulators, including NF-κB, Wnt/β-catenin, YAP, and MAPK, ultimately contributing to cell death, cellular senescence, matrix degradation, and sustained inflammation. From a therapeutic perspective, we summarize mechanobiologically informed strategies, including macromechanical modulation, signaling regulation, and advanced biomaterial platforms for mechanical support, viscoelastic regulation, lubrication, drug delivery, and immunomodulation, aimed at restoring mechanical homeostasis and supporting tissue regeneration.

We previously found that skin tone correlates with intronic polymorphisms influencing the expression of the Joubert Syndrome (JS) ciliopathy gene TMEM138 , suggesting that primary cilia might regulate pigment production in skin melanocytes. Herein, we show that many ciliary proteins regulate basal pigmentation in wild-type mouse and human melanocytes by facilitating primary cilium-dependent Melanocortin-1 receptor signaling, and downstream activation of the Microphthalmia transcription factor and melanogenic gene expression. Additionally, we identify an extra-ciliary moonlighting role for TMEM138 and other JS proteins in endolysosomal organization required for the biogenesis of melanosomes, the pigment-producing lysosome-related organelle in melanocytes. Our results provide new mechanistic insights into the physiological regulation of pigmentation and suggest that JS-specific pathology might be mediated by ciliary-independent mechanisms.

Primary cilia, which are present in most brain cells, are essential for brain development and function. During early brain development, dysfunction of the primary cilia can lead to a broad spectrum of disorders, collectively termed ciliopathies, that include brain malformations and intellectual disability. Although the role of primary cilia in brain development is well-established, cilia-mediated signaling in mature neurons and the contribution of cilia to neuronal circuit function remain controversial. Using mouse genetic and behavioral studies, single-cell electrophysiology, and 2-photon imaging, we show that deletion of primary cilia from adult hippocampal neurons is not required for hippocampal circuit function or behavior. Chronic genetic deletion or acute laser ablation of primary cilia from mature pyramidal neurons in the CA1 or CA3 regions of the hippocampus did not affect neuronal excitability, basal synaptic transmission, or long-term synaptic plasticity at excitatory CA3-CA1 hippocampal synapses. Moreover, the loss of primary cilia did not affect hippocampal-dependent learning and memory or anxiety-like behaviors. These results challenge the prevailing view of cilia function in mature hippocampal neurons and suggest that neuronal cilia in the adult hippocampus do not serve as major signaling hubs for pathways essential for neuronal function or behavior.