生物学最新文献

During development, spatial-temporally patterned tissue-level stresses and mechanical properties create diverse tissue shapes. To understand the mechanics of small-scale embryonic tissues, precisely controlled sensors and actuators are needed. Previously, we reported a control-based approach named tissue force microscopy (TiFM1.0), which combines dynamic positioning and imaging of an inserted cantilever probe to directly measure and impose forces in early avian embryos. Here, we present an upgraded system (TiFM2.0) that uses interferometer positioning to minimise probe holder footprint, enhancing accessibility and imaging signal. This new design enables a double-probe configuration for bidirectional stretching, compression and stress propagation experiments. As proof-of-concept, we showcase a variety of examples of TiFM2.0 applications in chicken and zebrafish embryos, including the characterisation of mechanical heterogeneities important for the morphogenesis of the chicken posterior body axis. We also present simplified designs and protocols for the replication of TiFM systems with minimal custom engineering for developmental biology labs.

Fracture - the initiation and propagation of cracks - has long been associated with structural failure. However, active living tissues often harness fracture as a controlled morphogenetic tool due to their unique capacities to self-organise and self-repair. In this Review, we highlight how fractures are actively interpreted, integrated and functionalised within developmental programmes to sculpt tissues across scales and species. We connect core concepts from fracture mechanics, such as stress concentration, energy release and fatigue, to biological contexts, showing how tissues actively adapt these principles by remodelling their adhesion, cytoskeleton and extracellular matrix. From reversible epithelial tears to permanent organismal fission, we discuss examples in which fracture contributes to morphogenesis, homeostasis, reproduction and egress. Further, we argue for an interdisciplinary approach to understanding how fractures emerge and drive morphogenetic transitions.

Peripheral nerve regeneration requires precise selection of the appropriate targets of innervation, often in an environment that differs from that during the developmental wiring of the neural circuit. Severed axons of the zebrafish posterior lateral line nerve have the capacity to reinnervate mechanosensory hair cells clustered in neuromast organs. Regeneration represents a balance between fasciculated regrowth of the axonal bundle and defasciculation of individual axons into the epidermis where neuromasts reside. The cues that guide pathfinding during regeneration of the posterior lateral line nerve are unknown. Here, we show that regenerating axons selectively defasciculate through distinct gaps in the epidermal boundary layer. We found that the gene col18a1a, which encodes the secreted heparan sulfate proteoglycan collagen XVIII, is expressed by the neuromast and by a subset of Schwann cells that are located at the points of axonal defasciculation. Furthermore, we observed aberrant axonal branching at inappropriate locations during nerve regeneration in col18a1a mutants. We propose a model in which collagen XVIII patterns the basement membrane to affect the precision of axonal navigation.

All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the Caenorhabditis elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. Loss of SCAV-2, a CD36 family scavenger receptor, restored LPR-3 matrix localization and suppressed the tube shaping defects of lpr-1 and a subset of pre-cuticle mutants, but not lpr-3 mutants. SCAV-2 accumulates at duct and pore apical surfaces and functions locally within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of the luminal aECM of the tube, possibly by acting as transporters of LPR-3 or an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.

Vesicle-associated membrane protein-associated protein A (VAPA) is a protein of the endoplasmic reticulum (ER) and a component of several membrane contact sites (MCSs). We show here that VAPA also localizes to the inner nuclear membrane (INM), in close proximity to nuclear lamins, INM proteins and nucleoporins. Using our proteomics approach 'rapamycin- and APEX-dependent identification of proteins by SILAC' (RAPIDS), we identified several nuclear proximity partners of VAPA, including emerin, different LAP2 isoforms, lamin A/C and Nup153. Depletion of VAPA in various cellular systems resulted in reduced nuclear lamin levels and aberrant nuclear morphology, including the formation of membrane invaginations and tunnels. Furthermore, histone acetylation levels were altered. Our data suggest that VAPA has distinct nuclear functions, in addition to its established role as an ER organizer.

Microtubule organization plays a central role in cell differentiation, orchestrating essential processes such as cell polarization, mechanotransduction, organelle positioning and intracellular transport. A hallmark of many differentiated cells is the transition from a centrosomal to a non-centrosomal microtubule-organizing center (MTOC). Here, we demonstrate that both centrosomal and nuclear envelope (NE)-associated MTOCs coexist in osteoclasts. We show that the key players for NE-MTOC formation, the AKAP6 and nesprin-1 (SYNE1) isoforms AKAP6β and nesprin-1α, previously considered muscle specific, are upregulated during osteoclast differentiation, suggesting a conserved role in NE-MTOC assembly across cell types. Targeted depletion of AKAP6 in RAW264.7-derived osteoclasts led to the displacement of the Golgi and MTOC-associated proteins PCM1, pericentrin and CDK5RAP2 from the NE, while their centrosomal localization remained intact. This selectively impaired microtubule nucleation from the NE without disrupting centrosomal microtubule activity, enabling a functional dissection of the two MTOCs. Loss of NE-MTOC activity, through AKAP6 depletion, impaired podosome formation and significantly reduced bone resorption capacity, highlighting the distinct and essential role of NE-derived microtubules in osteoclast function.

Regulation of lamin A/C levels and distribution is crucial for nuclear integrity and mechanotransduction via the linker of nucleoskeleton and cytoskeleton (LINC) complex. Dysregulation of lamin A/C correlates with poor cancer prognosis, and its levels determine sensitivity to the microtubule-stabilising drug paclitaxel. Paclitaxel is well-known for disrupting mitosis, yet it also reduces tumour size in slow-dividing tumours, indicating an additional, poorly characterised interphase mechanism. Here, we reveal that paclitaxel induces nuclear aberrations in interphase through SUN2-dependent lamin A/C disruption. Using advanced optical imaging and electron cryo-tomography, we show the formation of aberrant microtubule-vimentin bundles during paclitaxel treatment, which coincides with nuclear deformation and altered lamin A/C protein levels and organisation at the nuclear envelope. SUN2 is required for lamin A/C reduction upon paclitaxel treatment and is in turn regulated by polyubiquitylation. Furthermore, lamin A/C expression levels determine not only cell survival during treatment but also recovery after drug removal. Our findings support a model in which paclitaxel acts through both defective mitosis and interphase nuclear-cytoskeletal disruption, providing additional mechanistic insights into a widely used anticancer drug.

Within the nucleus of each human cell, ∼2 m of linear DNA is compacted and organized. The structures and principles of genome organization are developmentally regulated and broadly evolutionarily conserved. However, conclusive links between genome structure and function have been difficult to find. In this Review, we provide an overview of mammalian genome organization, highlight recent studies demonstrating how it interacts with evolutionary diversity, and explore its contributions to development. We propose an innovative perspective - that variability in genome organization supports plastic cell fates in multicellular organisms - and draw analogies to show how evolutionary variation can inform study of the function of genome organization.

In this study, the effects of Pseudomonas putida strain XMS-1 and its sodium alginate (SA)-producing gene algD deletion mutant (∆algD) on cadmium (Cd) immobilization in solution, and Cd availability and uptake in lettuce plants and mechanisms involved in the contaminated soils were investigated. Compared with XMS-1, ∆algD increased the solution Cd concentration by 57 % and reduced the cell surface-adsorbed and intracellular Cd contents by 44-57 % after 36 h of incubation. Compared with XMS-1, ∆algD significantly decreased the lettuce biomass, iron/manganese oxide- and organic matter-bound Cd contents, pH values, and polysaccharide and mineral-associated organic carbon contents and increased the exchange of Cd and lettuce leaf Cd contents in the soils. Furthermore, compared with XMS-1, ∆algD significantly reduced the relative abundances of Cd-immobilizing related abundant (Knoellia, Pseudomonas, Lysobacter, Microbacterium, and Flavisolibacter) and rare (Saccharothrix, Pajaroellobacter, Dyadobacter, Stenotrophomonas, Candidatus Koribacter, and Mumia) genera and functional genes mnxG, cumA, mnp, and epsA involved in manganese oxidation, ferromanganese nodule formation, and exopolysaccharide production in the rhizosphere soils of lettuce plants compared to XMS-1. Correlation analysis revealed negative relationships between the relative abundances of these bacterial populations and Cd uptake in lettuce tissues. These findings suggest the significant effects of algD in XMS-1 on reducing Cd availability and accumulation in lettuce through enriching the Cd-immobilizing related bacterial communities and functional genes in the contaminated soils. Our findings offer new insights into the mechanisms underlying algD-mediated reduction in Cd accumulation in lettuce by XMS-1, laying a crucial foundation for the use of SA-producing bacteria to ensure safe vegetable production in the Cd-contaminated soils.