Biology Open最新文献

Post-translational modifications (PTMs) of microtubules control many aspects of their functionality. Specifically, the C-terminal tails of α- and β-tubulin harbour a complex array of PTMs, including polyglutamylation and the reversible detyrosination/tyrosination. The spatial proximity of these two distinct sets of PTMs suggests the possibility of a functional cross-talk between polyglutamylation and (de)tyrosination. In this study, we employ gene deletion and overexpression of the enzymes tubulin-tyrosine ligase (TTL) and tubulin-tyrosine carboxypeptidase (VASH) to provide a detailed analysis of the effects of (de)tyrosination on the protozoan parasite Trypanosoma brucei. While the deletion of either of the enzymes is not lethal, cells exhibit subtle morphological defects, resulting from both hyper- and hypotyrosination. Additionally, hypertyrosination leads to defects in motility, characterised by an increase in tumbling motion. Using the TTL and VASH deletion cells in conjunction with our previously generated trypanosomes deficient in polyglutamylation, we uncovered a cross-talk between these two PTMs. The process of microtubule detyrosination enhances polyglutamylation, which, in turn, stimulates efficient detyrosination, thus establishing a positive feedback loop between these two PTMs.

Effective methods of anesthesia for octopuses are essential to physiological studies as well as for their welfare in scientific research. However, commonly used forms of general anesthesia using ethanol, magnesium chloride, and similar agents have certain drawbacks. While these methods effectively induce still states in the octopus, they also affect the peripheral body and nervous system and are therefore less than optimal for studying local behavior in octopus arms and suckers. Further, stupefying effects outlast the anesthetized state. We explore an old, rarely used method of octopus 'hypnosis' in which tonic immobility is induced as a complementary and sometime alternative method to general anesthesia, as well as being particularly suited to studies of local arm-sucker coordination. We modify the procedure for better handling, unimpeded respiration, and isolation of arm peripheral nervous system from the central nervous system (CNS). In the still state, an arm can be neurophysiologically isolated from the CNS by local Mg2+ injection, removing need for isolation by amputation. Exemplary studies of arm-sucker coordination and electrode placements are presented. Additionally, an intriguing phenomenon is observed where the induction of tonic immobility is notably diminished in cases of senescence. This modified procedure offers new convenience and directions for octopus neurobehavioral research.

Branching morphogenesis requires dramatic changes in cell polarity, proliferation, migration, and actin dynamics to elaborate tubular networks. However, little is known about how microtubules support these cell behaviors in 3D tissues. Using organotypic cultures, we first examined the organization of the microtubule cytoskeleton. Simple luminal epithelial cells exhibited non-centrosomal, apico-basally oriented microtubule arrays, while stratified luminal cells had centrosomally radiating microtubules. During collective migration, luminal cells adopted an ameboid-like organization with a rear-facing nuclear-centrosomal axis. Multiple staining approaches suggest that cells in the basal-most luminal cell layer had more stable microtubules than cells deeper within the stratified layer. Finally, we tested the requirement for microtubules using pharmacologic inhibitors. Both microtubule stabilization and destabilization prevented bud formation and arrested duct elongation. Cell tracking analysis demonstrated that microtubules coordinated luminal cell migration within elongating buds. Destabilizing microtubules reduced cell directionality, while stabilizing microtubules did not affect directionality but reduced cell motility. Our data reveal that microtubules are essential for collective migration of luminal cells and for mammary branching morphogenesis.

Prostate cancer management faces significant challenges in distinguishing indolent from aggressive disease, particularly since most patients are intermediate-risk and therefore hinders the ability to recommend standardized treatment recommendations. Moreover, current prognostic tools including Gleason scoring and tumor staging demonstrate limited accuracy for predicting disease progression and tumor recurrence. DNA methylation serves as a stable epigenetic modification that directly regulates gene expression, making it an ideal biomarker for cancer prognosis. Therefore, this study leveraged whole-genome enzymatic methylation sequencing on 120 patients to develop a novel prognostic signature for aggressive prostate cancer progression. We analyzed 20,849 differentially methylated regions (DMRs) and employed multiple machine learning approaches to identify optimal biomarkers. This revealed a 14-region DNA methylation signature that can serve as independent prognostic prediction factors outperforming traditional clinical indices. Further, when combined into a risk score it achieved a clinically meaningful odds ratio. This methylation-based approach provides actionable information for treatment decisions and surveillance strategies, representing a significant advancement toward precision medicine in prostate cancer management through biologically informed risk stratification.

Cleft lip with or without cleft palate (CL/P) represents one of the most common congenital craniofacial anomalies. Its complex genetic etiology remains incompletely understood. This study investigated compound inheritance of mutations in the EHHADH and MASP1 genes in a Polish family with three affected individuals using whole-genome sequencing and bioinformatic analysis, followed by zebrafish functional validation. We identified mutations in both genes that segregated with the CL/P phenotype. Network analysis demonstrated significant functional associations between these genes, with enrichment for innate immune response pathways. Using zebrafish models, we validated the phenotypic consequences of these mutations through mRNA injection experiments. Individual or combined injections of mutant EHHADH and MASP1 mRNAs resulted in craniofacial abnormalities, with co-injection producing the most severe phenotypes, including cleft formation. Alcian Blue staining revealed significant alterations in cartilage development, particularly in the ceratohyal angle and chondrocyte morphology. These changes may affect extracellular matrix composition and cartilage biomechanics, potentially disrupting the structural integrity and mechanical properties essential for proper craniofacial morphogenesis. Our findings suggest the possibility of a novel genetic mechanism for nonsyndromic CL/P involving the interaction between metabolic processes regulated by EHHADH and immune signaling pathways controlled by MASP1. This study expands our understanding of the genetic complexity underlying CL/P and highlights the potential intersection of immune regulation and metabolic processes in craniofacial development.

Water intakes entrain large numbers of fish larvae in waterways where drift coincides with large-scale extraction. While modern fish-protection screens can reduce these losses, many are not designed for larvae and were developed or evaluated primarily for juveniles and adults. This study evaluated the effectiveness of Australia's fish screen design criteria (which specify a maximum approach velocity of 0.1 m s-¹ and slot widths of 2-3 mm) for protecting drifting larval Murray cod (Maccullochella peelii). Larvae were tested in a large flume under combinations of approach velocity (0.1 or 0.2 m s-¹), slot width (2 or 3 mm), and proximity. Entrainment rose sharply with velocity; slot size had a smaller interactive effect. The most protective combination (0.1 m s-¹ and 2 mm) reduced entrainment by up to 94% relative to unscreened conditions. Three-dimensional flow measurements helped explain how velocity vectors interact to influence larval fate. The results demonstrate that Australia's current standards, although developed for juveniles, can provide strong larval protection when strictly followed, but that even modest departures can sharply increase risk. More broadly, since the criteria tested here are less conservative than those adopted in many other countries, where empirical evidence on larval behaviour does not exist, targeted research could determine whether existing guidelines warrant revision.

Hosted in the scenic surroundings of the High Tatras, the V4SDB Meeting 2025 represented the fourth biennial conference of the Visegrád Group Society for Developmental Biology. The meeting brought together over 170 researchers covering a multidisciplinary range of topics, from early development and organogenesis to non-traditional model systems and evo-devo, as well as stem cells and plasticity. With its numerous high-level talks and rich poster sessions, complemented by social and outreach activities, the meeting provided an excellent platform for networking, knowledge exchange, and initiating new collaborations. Moreover, the organizers arranged the Young Developmental Biologists Workshop, focused on data analysis, soft-skills training and community strengthening, which further enhanced early-career researchers' participation and support at the meeting. Altogether, the event underscored the V4SDB's commitment to nurturing the developmental biology community within the region.

Skeletal muscle formation involves the fusion of myocytes into precisely aligned, multinucleated myofibres. These fibres continue to grow through reiterative rounds of myocyte fusion, incorporating new myonuclei and supporting muscle growth, repair and regeneration over organismal life span. The vertebrate-specific myocyte fusogens, Myomaker (Mymk) and Myomixer (Mymx), are crucial for generating multinucleated skeletal muscles. Here, using quantitative imaging and a mymx knockout strain, we explored the impact on myogenesis at different life stages of the zebrafish. We demonstrate that during the initial phase of muscle formation, mymx has a spatiotemporally varied expression across all axes of the developing myotome, not just along the anterior-posterior axis. On Mymx loss, myotome morphogenesis is disrupted, with both cell and tissue structure impacted. In particular, the shape of the resulting myotome segments is altered. Moreover, we show differential effects of Mymk versus Mymx loss on myocyte fusion and muscle growth. Finally, we report that perturbation to adult muscle multinucleation and size impacted bone development, again with different phenotypic severities among the two fusogen mutants. Together, our work provides insights into the interplay between myocyte fusion, myotome morphogenesis and acquisition of final adult form.

The Genetics Society Non-Seed Plant meeting brought together researchers embracing the diversity of plants and using emerging and established model systems covering hornworts, mosses, liverworts, lycophytes and ferns. This growing community of researchers is exploring fundamental questions on plant development, evolution and environmental responses. Highlights included cutting-edge work in bryophytes on meristem development, hormonal signalling and chromatin regulation, as well as advances in charophyte algae, illuminating the evolutionary origins of key plant traits. The meeting emphasized how non-seed plants, often overlooked in mainstream plant science, are now providing transformative insights into gene regulation, plant-environment interactions and crop improvement potential. These developments reflect a broader shift in plant biology, where diverse model systems are essential for reconstructing the evolutionary history of plants and addressing modern agricultural challenges.