Cell and Tissue ResearchPub Date : 2025-10-01Epub Date: 2025-07-29DOI: 10.1007/s00441-025-03992-0
Sara Vega-Torreblanca, Diana Cristina Pinto-Dueñas, Christian Hernández-Guzmán, Dolores Martín-Tapia, Lourdes Alarcón, Bibiana Chávez-Munguía, Lizbeth Salazar-Villatoro, Sirenia González-Pozos, Josué David Hernández-Varela, Leticia Ramírez-Martínez, Esther López-Bayghen, José Jorge Chanona-Pérez, Lorenza González-Mariscal
{"title":"ZO-2 is a scaffold at the centriole and mitotic spindle poles that enhances microtubule stability and supports the proper development of mitotic spindles and cilia.","authors":"Sara Vega-Torreblanca, Diana Cristina Pinto-Dueñas, Christian Hernández-Guzmán, Dolores Martín-Tapia, Lourdes Alarcón, Bibiana Chávez-Munguía, Lizbeth Salazar-Villatoro, Sirenia González-Pozos, Josué David Hernández-Varela, Leticia Ramírez-Martínez, Esther López-Bayghen, José Jorge Chanona-Pérez, Lorenza González-Mariscal","doi":"10.1007/s00441-025-03992-0","DOIUrl":"10.1007/s00441-025-03992-0","url":null,"abstract":"<p><p>Previous studies revealed the presence of several tight junction (TJ) proteins in the centrosome and their interaction with various centriolar proteins, prompting us to analyze whether this also applies to the TJ protein ZO-2. Here, we found that ZO-2 colocalizes with CEP164 in the distal appendage of the mother centriole and is also present in the pericentriolar region, mitotic spindle poles, the basal body of primary cilia, and the tail of spermatozoa. The absence of ZO-2 altered the cellular content of centriolar proteins CEP164, centriolin, and CEP135, but did not change the morphology of centrioles. ZO-2 depletion inhibits the development of astral and mitotic spindle microtubules expressing EB1. At the spindle poles, ZO-2 depletion increases the accumulation of NuMA while reducing the levels of kinesin KIF14 and the TPX2 scaffold, and the accumulation of the kinase p-Aurora, leading to a decrease in mitotic spindle length, microtubule instability, and abnormal chromosome congression. KIF14, NuMA, and p-Aurora co-immunoprecipitate with ZO-2, and NuMA and Aurora-A bind to different segments of ZO-2. At the ciliary basal body, ZO-2 depletion reduces the content of CEP164, KIF14, and IFT-B protein IFT57, while increasing the expression of p-Aurora and pAKT. These changes block primary cilium development and the response to Sonic Hedgehog signaling pathway stimulation. These results suggest that, rather than being a centrosomal architectural component, ZO-2 enhances microtubule stability and serves as a scaffold that facilitates the adequate accumulation of spindle pole and centriole proteins, allowing proper poleward spindle microtubule flux and cilia development.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"21-50"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell and Tissue ResearchPub Date : 2025-10-01Epub Date: 2025-09-01DOI: 10.1007/s00441-025-04003-y
Wafaa Mahmoud, Alexander Perniss, Krupali Poharkar, Maryam Keshavarz, Ulrich Gärtner, Johannes Oberwinkler, Burkhard Schütz, Thomas Worzfeld, Stefan Offermanns, Wolfgang Kummer
{"title":"Differential expression of villin and advillin by neuroendocrine and tuft cells in the murine lower airways.","authors":"Wafaa Mahmoud, Alexander Perniss, Krupali Poharkar, Maryam Keshavarz, Ulrich Gärtner, Johannes Oberwinkler, Burkhard Schütz, Thomas Worzfeld, Stefan Offermanns, Wolfgang Kummer","doi":"10.1007/s00441-025-04003-y","DOIUrl":"10.1007/s00441-025-04003-y","url":null,"abstract":"<p><p>Previous studies identified a rare cell type in the mouse tracheal epithelium with immunoreactivity to the microvillus protein villin (Vil1), which persisted in mice lacking tuft cells due to deletion of the transcription factor Pou2f3. This study aimed to clarify the identity of this ill-defined cell type. Ultrastructurally, all cells with tightly packed microvilli observed in the tracheal epithelium of Pou2f3<sup>-/-</sup>-mice contained basally located dense core vesicles, a characteristic feature of neuroendocrine cells (NEC). Accordingly, immunofluorescence double-labeling utilizing NEC markers revealed villin-labeling in two thirds of NEC in the trachea, a reporter mouse strain showed Cre recombinase activity driven by the Vil1 promoter in a subpopulation of tracheal NEC, and analysis of single cell RNA sequencing data revealed Vil1-mRNA expression by tracheal NEC. Notably, only a minimal fraction (≈1%) of bronchopulmonary NEC (solitary and clustered in neuroepithelial bodies) displayed villin-immunoreactivity, despite nearly half of them having a history of Vil1 promoter activity. Microvilli of tuft cells differed ultrastructurally from those of NEC, and the majority of tuft cells were immunoreactive to advillin (Avil), showed Avil promoter activity as indicated by a reporter mouse strain, and expressed Avil-mRNA in the sequencing data set. This study uncovers villin-expressing cells in the lower airways as a cell population hidden among NEC. Advillin, not villin, is identified as a marker for airway tuft cells. This should be considered in interpreting findings based on the use of villin as a marker or Cre-driver when investigating rare cells in the murine airways.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"1-20"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aoife Smyth, Breedge Callaghan, Mustapha Irnaten, Darrell Andrews, Colin E Willoughby, Colm O'Brien
{"title":"MicroRNA-29b targets ADAM12 and 19 to regulate the extracellular matrix in lamina cribrosa cells.","authors":"Aoife Smyth, Breedge Callaghan, Mustapha Irnaten, Darrell Andrews, Colin E Willoughby, Colm O'Brien","doi":"10.1007/s00441-025-04006-9","DOIUrl":"https://doi.org/10.1007/s00441-025-04006-9","url":null,"abstract":"<p><p>Glaucoma remains the leading cause of irreversible blindness worldwide, with elevated intraocular pressure (IOP) being the only modifiable risk factor in primary open-angle glaucoma (POAG). Despite adequate IOP control, many patients continue to progress to irreversible optic neuropathy, emphasising the need for alternate treatments. Transforming growth factor-beta (TGF-β) promotes extracellular matrix (ECM) production and fibrosis at the optic nerve head (ONH) in glaucoma. A disintegrin and metalloprotease-12 and metalloprotease-19 (ADAM12 and ADAM19) are implicated in fibrosis. Recent studies have explored miRNA-based manipulation of the TGF-β signalling pathway as a potential therapeutic strategy in fibrosis. This study investigates whether miR-29b modulation affects ADAM12, ADAM19, and ECM gene expression in human lamina cribrosa (LC) cells. Primary human normal lamina cribrosa (NLC) and glaucoma LC (GLC) cells were treated with TGF-β1 and transfected with either a miR-29b mimic or control. Gene expression levels of ADAM12, ADAM19, miR-29b, and several ECM genes were quantified using real-time RT-qPCR, and protein expression levels by Western blotting. ADAM12 and ADAM19 expression was elevated in untreated GLC cells, and treatment with TGF-β1 in both NLC and GLC cells increased ADAM12 and ADAM19 expression. The expression of miR-29b was significantly reduced in both GLC- and TGF-β1-treated NLC and GLC cells. Transfection with miR-29b resulted in a marked reduction in ADAM12 and ADAM19 mRNA expression in TGF-β1-treated NLC and GLC cells. Additionally, miR-29b transfection reduced ECM gene expression in both NLC and GLC under TGF-β1 stimulation. Our results demonstrate that miR-29b plays a crucial role in fibrotic remodelling at the LC by antagonising the effects of TGF-β1 on ADAM and ECM gene expression, representing a novel therapeutic target in glaucoma.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lenka Rouhová, Gabriela Krejčová, Ana Beatriz Barletta Ferreira, Houda Ouns Maaroufi, Fernando G Noriega, Carolina Barillas-Mury, Hana Sehadová, Marcela Nouzova
{"title":"Developmental changes in the Aedes aegypti mosquito endocrine gland complex.","authors":"Lenka Rouhová, Gabriela Krejčová, Ana Beatriz Barletta Ferreira, Houda Ouns Maaroufi, Fernando G Noriega, Carolina Barillas-Mury, Hana Sehadová, Marcela Nouzova","doi":"10.1007/s00441-025-04012-x","DOIUrl":"https://doi.org/10.1007/s00441-025-04012-x","url":null,"abstract":"<p><p>In the larvae of the mosquito Aedes aegypti, the three most important endocrine glands, the corpora allata (CA), the corpora cardiaca (CC), and the prothoracic gland (PG), together form the glandular complexes (GC). Using confocal laser scanning microscopy in combination with immunohistochemistry, in situ hybridization, ultrastructural expansion microscopy, and apoptosis studies, we were able to identify the different cell types of the GC and follow their fate during metamorphosis. Our studies revealed that the CC is not a well-defined organ but consists of individual cells randomly distributed within the GC and CA-CC complexes. Furthermore, imaging and in situ hybridization show that the CA is a compact organ composed of a single cell type. We observed that CA and CC survive during the larval-to-adult transition, while PG undergoes apoptosis and disappears within the first 24 h of adult life. This study lays the foundation for a more detailed understanding of the structure and changes in the major endocrine organs of mosquitoes, which are vectors of several important infectious diseases.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cole J Meier, Shabbir Ahmed, Tania Y Estévez-Lao, Julián F Hillyer
{"title":"Phagocytic hemocytes, independent of pericardial cells, modulate cellular immune responses on the dorsal vessel of mosquitoes, including the infection-induced reduction of the heart rate.","authors":"Cole J Meier, Shabbir Ahmed, Tania Y Estévez-Lao, Julián F Hillyer","doi":"10.1007/s00441-025-04011-y","DOIUrl":"https://doi.org/10.1007/s00441-025-04011-y","url":null,"abstract":"<p><p>Infection induces the aggregation of hemocytes on the dorsal vessel of mosquitoes. These hemocytes, called periostial hemocytes, phagocytose pathogens and produce immune factors on the abdominal portion of the dorsal vessel, called the heart. One of these immune factors, nitric oxide, is a pleiotropic free radical that is an antimicrobial and a heartbeat reducer. But nitric oxide is not just produced by hemocytes. It is also synthesized by pericardial cells that flank the heart, and other tissues. To determine whether it is the periostial hemocytes or the pericardial cells that modulate the heart following infection, we chemically ablated the hemocytes using clodronate liposomes and measured immune responses and heart physiology. We demonstrate that clodronate liposomes ablate the sessile hemocytes, including the periostial hemocytes, while leaving the pericardial cells and heart integrity unaffected. Moreover, ablating hemocytes abolishes the phagocytosis of bacteria, alters the deposition of melanized bacteria, and decreases nitric oxide synthase activity on the heart. Importantly, hemocyte ablation eliminates the infection induced reduction of the heart rate, mainly by modifying the anterograde heart rate. Therefore, periostial hemocytes drive immune responses on the heart and infection-induced changes to circulatory physiology.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Catecholaminergic system in the brain of the terrestrial slug Limax valentianus.","authors":"Ryota Matsuo, Aika Matsuki, Yuko Matsuo","doi":"10.1007/s00441-025-04010-z","DOIUrl":"https://doi.org/10.1007/s00441-025-04010-z","url":null,"abstract":"<p><p>Catecholamines, including dopamine, are thought to play important roles in the nervous system of mollusks. In the brains of the terrestrial gastropods, the procerebrum is the higher olfactory center involved in olfactory associative learning. Dopamine is known to affect the activities of interneurons in the procerebrum. However, little is known about from where and how dopaminergic neurons project to the procerebrum. In the present study, we generated a specific antibody against tyrosine hydroxylase (TH) and visualized catecholaminergic neurons, including dopaminergic neurons, in the central and peripheral nervous systems of the terrestrial slug Limax valentianus. We found that (1) the number of the cell bodies of catecholaminergic neurons was larger in the ventral aspect than in the dorsal aspect of the brain; (2) most of the TH-immunoreactive putative sensory afferents in the superior tentacle projected to the brain along the axis as bundles in a regularly spaced manner while bypassing the procerebrum following entry into the brain; (3) TH-immunoreactive nerves in the procerebrum were derived from at least three distinct origins outside and within the procerebrum; and (4) dopamine upregulated the oscillatory frequency of the local field potential oscillation in the procerebrum, which was occluded by pre-incubation with sulpiride, a mammalian D<sub>2</sub>/D<sub>3</sub> receptor antagonist. This is the first study to investigate the catecholaminergic system, with a special focus on the procerebrum, using a specific antibody against TH in terrestrial gastropods. The present study uncovered catecholaminergic regulation of procerebrum activity through innervation from both the outside and inside of the procerebrum.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniela J Sasovsky, Gabriela B Olea, Gonzalo Ojeda, Angélica M Cesario, Franco J Gonzalez, Bruno Lomonte, Daniel Lombardo, Soledad Bustillo
{"title":"Exploring the antiangiogenic effects of Phospholipases A<sub>2</sub> from Bothrops diporus venom.","authors":"Daniela J Sasovsky, Gabriela B Olea, Gonzalo Ojeda, Angélica M Cesario, Franco J Gonzalez, Bruno Lomonte, Daniel Lombardo, Soledad Bustillo","doi":"10.1007/s00441-025-04008-7","DOIUrl":"https://doi.org/10.1007/s00441-025-04008-7","url":null,"abstract":"<p><p>Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a crucial process in both physiological and pathological contexts, including cancer. Phospholipases A<sub>2</sub> (PLA<sub>2</sub>s), enzymes found in snake venoms, have attracted attention due to their potential antiangiogenic properties. In this study, we explored the antiangiogenic effects of PLA<sub>2</sub> isoforms isolated from Bothrops diporus venom using a combination of in vivo and ex vivo models. The chorioallantoic membrane (CAM) assay revealed a significant reduction in vascular density and branching following PLA<sub>2</sub>s treatment, with histological analysis confirming vascular regression, including vessel wall thinning and luminal collapse. Moreover, PLA<sub>2</sub>s induced endothelial cell apoptosis, as shown by TUNEL staining, and reduced VEGF expression. The filter paper disc variant of the CAM assay further supported these findings, demonstrating inhibited neovascularization while preserving mature vessels. Additionally, the CAM explant assay showed a marked decrease in vascular complexity and branching. These results demonstrate the antiangiogenic effect of PLA<sub>2</sub> isoforms from B. diporus and suggest that these enzymes may modulate key angiogenic pathways. Based on our previous findings, this modulation may involve interference with integrin-mediated signaling, which could underlie the vascular effects observed. Thus, this work provides compelling evidence for the potential role of snake venom-derived PLA<sub>2</sub>s in modulating angiogenesis and highlights the need for further research into their mechanisms and possible biomedical applications.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Parvin is essential for indirect flight muscle (IFM) performance and Zasp52 localisation to the Z-disc in Drosophila melanogaster.","authors":"Ushashi Ain, Benazir Fatma, Hena Firdaus","doi":"10.1007/s00441-025-04007-8","DOIUrl":"10.1007/s00441-025-04007-8","url":null,"abstract":"<p><p>The integrin-associated proteins (IAPs) function in a tightly regulated and coordinated manner to maintain the complex cytoarchitecture at the myotendinous junctions (MTJs) of Drosophila indirect flight muscles (IFMs). Parvin, a conserved but less explored IAP, forms a ternary complex with ILK and PINCH (the IPP complex). Although the IPP complex is functionally conserved, playing a central role in integrin-mediated adhesion, its individual components may also exert independent roles. The present study investigates parvin as a critical regulator of IFM function and sarcomeric integrity. Downregulation of parvin in IFM leads to altered sarcomere organisation and lowered accumulation of essential thin filament genes, including Act88F, wupA, up, TpnC4, and TM2 transcripts. Furthermore, Z-disc-associated proteins such as Zasp52 and its binding partner α-actinin, which are vital for myofibril stability, showed markedly reduced expression in parvin-deficient muscles. Notably, Zasp52 failed to localise to the Z-discs in IFMs, despite being detectable in leg muscles, suggesting tissue-specific mislocalisation. The expression of sallimus, a titin orthologue contributing to muscle elasticity, remained unchanged. Our findings underscore parvin's essential role in preserving IFM ultrastructure and function. We also emphasise the importance of maintaining the stoichiometric balance within the IPP complex-including its extended member Ras suppressor 1 (RSU1)-for proper muscle performance. Additionally, perturbation of parvin expression in a tissue-specific manner revealed its broader role in fly viability and muscle-driven behaviours, including larval locomotion and leg muscle function. Collectively, this study positions parvin as a pivotal component in maintaining muscle integrity across multiple muscle types in Drosophila.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Beta-arrestin 1 is involved in the catabolic response stimulated by hyaluronan degradation in mouse chondrocytes.","authors":"","doi":"10.1007/s00441-025-03990-2","DOIUrl":"10.1007/s00441-025-03990-2","url":null,"abstract":"","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"341"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}