Biology Open最新文献

The India EMBO lecture course 'RNA-protein complexes: from molecular assembly to physiological functions and disease' was held at The National Centre for Cell Science, Pune, India, from February 24 to 28, 2025. The major theme of the lecture series centred on the recent advances in RNA-protein interactions and their role in regulating complex assembly or condensation as well as cellular functions and plasticity. Additionally, the course highlighted the impact of dysregulated post-transcriptional processes in various diseases. Speakers from various biological disciplines presented their research on both the fundamental architecture of RNA and protein complexes and their contributions to higher-order cellular functions. The course also featured flash talks and poster presentations selected from abstract submissions, alongside special methodological workshops on omics and phase separation. This Meeting Review reflects on the event's key discussions, drawing attention to the overarching themes and main conclusions.

Correct development of the testis serves as a springboard for male fertility in adult life, yet our understanding of the timing of human Sertoli and germ cell maturation and their dynamics is incomplete. To map the developmental timeline of germ cells and Sertoli cells, we analysed an extensive set of human foetal and prepubertal testicular samples [n=48, spanning from 7 post conception weeks (PCW) to 13.5 years of age]. Octamer binding transcription factor (OCT)3/4+ gonocytes were identified as the main source of proliferative germ cells during foetal development, while melanoma associated antigen (MAGE)-A4+ (pre)spermatogonia divided at a slow rate both in utero and during childhood. In samples aged between 4 and 10 years, anti-Müllerian hormone (AMH) expression is reduced and androgen receptor (AR) expression is increased, consistent with maturation of testicular Sertoli cells. Sertoli cell proliferation peaked at 2-2.5 years and gradually declined through early childhood, becoming minimal from the age of 6, coinciding with lumen formation. These data suggest that Sertoli cell maturation precedes the initiation of spermatogenesis well before the start of puberty. Ultimately, this human testicular developmental timeline serves as a reference for the development of in vitro gametogenesis models and paves the way for fertility preservation and restoration for those at risk of infertility.

The International Dutch Embryo Model Meeting took place at Radboud University in Nijmegen, the Netherlands, on March 27 and 28, 2025. This year's meeting, which was previously held twice as a Dutch event, served as a platform to discuss the progress made in studying embryonic development using in vitro embryo-like structures. Organised into sessions on pluripotency, blastoids, gastruloids, and gametes, the meeting featured presentations by invited (inter)national speakers. These talks were complemented by shorter presentations from academics and industry professionals, as well as poster presentations interspersed between sessions. The meeting included an interactive ethics session that explored the opportunities and risks of researching embryos and embryo-like structures. This Meeting Review aims to provide an overview of the first International Dutch Embryo Model Meeting by highlighting the topics discussed by leading experts in embryo modelling.

Coordinated cell polarity and force-responsive protein localization are essential for tissue morphogenesis, yet how embryonic cells sense forces and respond to mechanical cues remains a challenging question. Afadin- and α-actinin-binding protein (ADIP) has been implicated in microtubule minus-end anchoring, centrosome maturation and ciliogenesis. ADIP is also proposed to associate with the actomyosin cortex and regulate collective cell migration. ADIP behaves as a mechanosensitive planar cell polarity (PCP) protein when overexpressed in Xenopus embryos, but the distribution and regulation of endogenous ADIP has been unknown. Here we show that ADIP is present in early ectoderm as randomly distributed puncta that rapidly reorganize and polarize during epithelial wound repair. Endogenous ADIP also becomes enriched and planar polarized in the anterior neural plate towards the midline, consistent with its regulation by mechanical forces that operate during neural tube closure. ADIP polarization is attenuated by depletion of the core PCP component Diversin/Ankrd6, in agreement with the proposed interaction between the two proteins during PCP establishment. Finally, pharmacological disruption of microtubules, F-actin, and nonmuscle myosin II eliminates ADIP polarization in the neuroectoderm, indicating roles for microtubules and actomyosin networks in PCP. Together, these findings suggest that endogenous ADIP senses mechanical cues via the cytoskeletal machinery and functions in a context-dependent manner to control collective cell behaviors during vertebrate morphogenesis.

The Notch signaling pathway is crucial for germline stem cell (GSC) regulation in Caenorhabditis elegans, yet the molecular and biological consequences of GLP-1/Notch mutations remain poorly understood. This study systematically analyzes commonly used and pathological glp-1 loss- (lf) and gain-of-function (gf) mutations to investigate their effects on Notch activity at nascent transcript (ATS), mRNA, and germline levels. Using complementary direct readouts of Notch activation, including sygl-1 activation sites, mRNA levels, and germline functional assays of the Notch-responsive GSC pool and progenitor zone (PZ), we demonstrate that the severity of glp-1 mutations is dependent on their position within the GLP-1 protein. Among the commonly used glp-1 alleles we examined, NICD mutations reduced Notch transcriptional activation at cellular and germline levels while having little impact at the chromosomal (ATS) level, whereas partial lf NECD mutations have minimal effects across all biological levels. Furthermore, a series of regression analyses of sygl-1 activation, mRNA production, and PZ size reveal strong correlations, qualifying these readouts as predictive markers for germline function. These findings provide a comprehensive framework for understanding glp-1 mutation effects and offer new insights into the regulation of Notch signaling in stem cell biology.

Antibiotic treatment is often necessary to eliminate life-threatening bacterial infections. However, these treatments can alter production of bacterial extracellular vesicles (BEVs), which often contain pro-inflammatory biomolecules. In this study, we examined how the clinically-relevant antibiotics meropenem, tobramycin, and ciprofloxacin impacted BEV production from a urinary tract infection-associated Escherichia coli strain (CFT073 [WAM2267]) and a meningitis-associated strain (K1 RS218). BEVs from both strains caused a dose-dependent increase in expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells, priming the endothelium for interactions with immune cells. Blockade of toll-like receptor 4 revealed that this receptor was responsible for BEV-endothelial interactions. Treatment with meropenem, a β-lactam antibiotic, increased production of BEVs from strain K1 RS218. Furthermore, meropenem treatment caused strain CFT073 [WAM2267] to produce BEVs with heightened stimulatory capacity, possibly by amplifying the content of lipoprotein Lpp in these BEVs as measured by mass spectrometry. To our knowledge, this is the first study examining the interplay between antibiotic treatment and the effects of the resulting BEVs on endothelial ICAM-1 expression. Our results indicate treatment risks of certain antibiotics against specific strains of E. coli and could help identify therapeutic targets to reduce BEV-mediated endothelial stimulation during infection.

The Hippo signaling pathway is conventionally known to restrict tissue growth in animals. Genetic studies have also shown that loss of Hippo pathway components leads to defects in asymmetric cell division in Drosophila neural stem cells, known as neuroblasts. The hallmark of neuroblast division is the asymmetric localization of aPKC/Bazooka (Par3)/Par6 complex, termed the Par complex, to the apical cell cortex. However, the localization of the Hippo pathway components in neuroblasts remains unknown. Here, we report that two key activators of the Hippo pathway, Kibra and Salvador, polarize to the apical cortex of mitotic neuroblasts. We show that apical polarity, via the activity of aPKC, and F-actin dynamics synergize to drive Kibra polarization. Together, these results provide further insights into the relationship between apical polarity and Hippo pathway organization and suggest a possible mechanism by which pathway activity is regulated during neuroblast asymmetric division.

Unpredictability of the environments can shape not only the mean behavioral expression but also the structure of behavioral variance within wild populations. Yet, empirical tests integrating individual variation, trait covariances, and correlated plasticities across ecologically relevant gradients remain rare, particularly those aimed at phenotype integration. Using wild zebrafish, we examined how long-term exposure to turbidity and immediate changes in water clarity influence behavioral means, individual (co)variances, and plasticity integration across three coping behaviors-activity, aggression, and boldness. Adult fish were conditioned in clear and turbid water for a month, followed by repeated behavioral tests in clear as well as in turbid water. Individuals, maintained in clear or turbid water for a month, when exposed to perturbations in the water-clarity showed substantial variation in their behavioral adjustments. Mean behaviors changed primarily in response to immediate change in water turbidity and trial repetition, not long-term conditioning. However, conditioning strongly altered individual variance structure: turbid-conditioned individuals showed reduced consistency across testing waters, indicating greater behavioral flexibility under sensory uncertainty. The only evidence to behavioral syndromes was between activity and boldness [r= -0.379] among clear-conditioned treatment, whereas within-individual correlations between aggression and boldness were prominent in turbid-conditioned fish. Despite substantial variation in behavioral plasticity, we detected no among-individual correlations in plasticity across traits. Together, these results demonstrate that turbidity modulates multi-scale behavioral variation, influencing how traits covary and integrate within individuals, and highlight how environmental unpredictability shapes flexibility in coping strategies.

It has been shown that changes in plant flowering times are directly tied to climate change, often being the first and most visible indicators of broader, ecosystem-wide change. Despite this, tropical latitudes have been markedly understudied. We analyzed 19 tropical species across seven locations from 1960 to 2021. Through a series of Bayesian regression analyses of flowering date on maximum temperature, minimum temperature, and precipitation, we found that flowering dates of tropical plants have changed substantially with changes in climate. Flowering dates have shifted an average of 6.9 days per °C of maximum temperature change, 4.5 days per °C of minimum temperature change, and 0.28 days per mm precipitation. We then computed combined effects of the aforementioned climate variables and found that flowering dates have shifted 15.0 days per unit of combined temperature and precipitation changes (computed as the sum of products of standardized changes in climate variables and their posterior effect estimates). We found no meaningful difference in magnitude of change in flowering of species in consistently hot and wet locations to those in locations with seasonal wet and dry periods (Wilcoxon rank sum p>0.05). Our study demonstrates tropical ecosystems are not insulated from the impacts of climate change.

Precise genome editing remains a major challenge in functional genomics, particularly for generating knock-in (KI) alleles in model organisms. Here, we introduce the mini-golden system, a versatile Golden Gate-based subcloning platform that enables rapid assembly of donor constructs containing homology arms and a gene of interest. This system offers a library of middle entry vectors including diverse genes, enhancing the preparation of donor minicircles for KI applications. Using the mini-golden system, we efficiently generated a foxd3CreER KI zebrafish line, allowing conditional recombination in neural crest cells. To further improve genome editing precision, we developed a synthetic exon-based donor template strategy combined with fluorescence screening. Using this approach, we successfully engineered a targeted isoleucine-to-valine substitution (Ile-to-Val) in hbaa1.2, one of the two adult hemoglobin alpha genes in zebrafish. Importantly, despite the high sequence similarity between hbaa1.2 and its paralog hbaa1.1, our strategy specifically edited hbaa1.2, demonstrating the effectiveness of the synthetic exon approach. This method minimized undesired recombination and significantly improved the identification of lines carrying the edited genome. Together, we provide a robust toolkit for efficient and precise genome engineering in zebrafish, with broad applicability to other model systems.