Open Biology最新文献_第10页

The pivotal role of osteopontin in UV-induced skin inflammation in a mouse model. 在小鼠模型中，骨素在紫外线诱发的皮肤炎症中发挥了关键作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1098/rsob.230397

Haesoo Kim, Chang-Yup Shin, Chi-Hyun Park, Dong Hun Lee, Si-Hyung Lee, Jin Ho Chung

{"title":"The pivotal role of osteopontin in UV-induced skin inflammation in a mouse model.","authors":"Haesoo Kim, Chang-Yup Shin, Chi-Hyun Park, Dong Hun Lee, Si-Hyung Lee, Jin Ho Chung","doi":"10.1098/rsob.230397","DOIUrl":"10.1098/rsob.230397","url":null,"abstract":"Osteopontin (OPN) is a pro-inflammatory protein that influences bone remodelling, wound healing, angiogenesis, allergic inflammation, and skin diseases such as psoriasis, contact dermatitis and skin cancer. However, the role of OPN in the skin remains unclear. Therefore, this study aimed to investigate the role of OPN in the skin, particularly in the context of ultraviolet (UV) irradiation-induced inflammation. OPN expression and its effects on inflammatory modulators were assessed in human skin, in a mouse model and in vitro, using a UV source emitting both UVB and UVA radiation, which collectively contribute to UV-induced skin inflammation. OPN expression increased in human and mouse skin after UV irradiation. Compared with wild-type mice, UV irradiation-induced skin phenotypes, such as erythema and skin thickening, were alleviated in OPN-/- mice. In addition, the number of immune cells recruited to the skin after UV irradiation and the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) were observed to be decreased in the skin of OPN-/- mice compared with that of wild-type mice. By contrast, the degree of skin inflammation was higher in the hOPN KI mice than in wild-type mice. Treatment with recombinant OPN increased the expression of MMP-1 and inflammatory cytokines in human dermal fibroblasts and epidermal keratinocytes in vitro. Our results suggest that OPN may play a regulatory role in UV-induced skin inflammation.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 11","pages":"230397"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624322","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}

引用次数: 0

Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus. Moesin 通过与细胞核中 Mediator 复合物的 Med15 亚基直接结合，促进热休克基因的反应。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1098/rsob.240110

Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos

{"title":"Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.","authors":"Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos","doi":"10.1098/rsob.240110","DOIUrl":"10.1098/rsob.240110","url":null,"abstract":"The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240110"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366072","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}

引用次数: 0

Cell cycle visualization tools to study cardiomyocyte proliferation in real-time. 用于实时研究心肌细胞增殖的细胞周期可视化工具。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240167

Rustem Salmenov, Christine Mummery, Menno Ter Huurne

{"title":"Cell cycle visualization tools to study cardiomyocyte proliferation in real-time.","authors":"Rustem Salmenov, Christine Mummery, Menno Ter Huurne","doi":"10.1098/rsob.240167","DOIUrl":"10.1098/rsob.240167","url":null,"abstract":"Cardiomyocytes in the adult human heart are quiescent and those lost following heart injury are not replaced by proliferating survivors. Considerable effort has been made to understand the mechanisms underlying cardiomyocyte cell cycle exit and re-entry, with view to discovering therapeutics that could stimulate cardiomyocyte proliferation and heart regeneration. The advent of large compound libraries and robotic liquid handling platforms has enabled the screening of thousands of conditions in a single experiment but success of these screens depends on the appropriateness and quality of the model used. Quantification of (human) cardiomyocyte proliferation in high throughput has remained problematic because conventional antibody-based staining is costly, technically challenging and does not discriminate between cardiomyocyte division and failure in karyokinesis or cytokinesis. Live cell imaging has provided alternatives that facilitate high-throughput screening but these have other limitations. Here, we (i) review the cell cycle features of cardiomyocytes, (ii) discuss various cell cycle fluorescent reporter systems, and (iii) speculate on what could improve their predictive value in the context of cardiomyocyte proliferation. Finally, we consider how these new methods can be used in combination with state-of-the-art three-dimensional human cardiac organoid platforms to identify pro-proliferative signalling pathways that could stimulate regeneration of the human heart.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240167"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392239","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}

引用次数: 0

Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants. 组成型表达的 T 细胞共抑制受体 BTLA 和 CD5 之间的内部调节与近期胸腺移居者的耐受性。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240178

Adeolu O Adegoke, Govindarajan Thangavelu, Ting-Fang Chou, Marcos I Petersen, Kiyokazu Kakugawa, Julia F May, Kevin Joannou, Qingyang Wang, Kristofor K Ellestad, Louis Boon, Peter A Bretscher, Hilde Cheroutre, Mitchell Kronenberg, Troy A Baldwin, Colin C Anderson

{"title":"Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants.","authors":"Adeolu O Adegoke, Govindarajan Thangavelu, Ting-Fang Chou, Marcos I Petersen, Kiyokazu Kakugawa, Julia F May, Kevin Joannou, Qingyang Wang, Kristofor K Ellestad, Louis Boon, Peter A Bretscher, Hilde Cheroutre, Mitchell Kronenberg, Troy A Baldwin, Colin C Anderson","doi":"10.1098/rsob.240178","DOIUrl":"10.1098/rsob.240178","url":null,"abstract":"Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of Btla demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240178"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546637","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}

引用次数: 0

Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks. 性别作为老化过程中的一个生物变量：对分子和细胞特征的认识和展望。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240177

José Héctor Gibrán Fritz García, Claudia Isabelle Keller Valsecchi, M Felicia Basilicata

引用次数: 0

SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation. SLMAP3 通过涉及初级纤毛形成的机制对器官形成至关重要。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-17 DOI: 10.1098/rsob.240206

Ana Paula Dias, Taha Rehmani, Billi Dawn Applin, Maysoon Salih, Balwant Tuana

{"title":"SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation.","authors":"Ana Paula Dias, Taha Rehmani, Billi Dawn Applin, Maysoon Salih, Balwant Tuana","doi":"10.1098/rsob.240206","DOIUrl":"10.1098/rsob.240206","url":null,"abstract":"SLMAP3 is a constituent of the centrosome and is known to assemble with the striatin-interacting phosphatase and kinase (STRIPAK) complex, where it has been reported to repress Hippo signalling. The global knockout of SLMAP3 in mice results in embryonic/perinatal lethality and stunted growth without changes in the phosphorylation status of YAP. Diverse phenotypes present in the SLMAP3-/- embryos include reduced body axis, small and abnormal organs resembling defects in planar cell polarity (PCP) signalling, while also displaying the notable polycystic kidneys, a known manifestation of ciliopathies. Analysis of cell polarity in primary mouse embryonic fibroblasts (MEFs) including cell migration, orientation and mitotic spindle angle did not reveal any changes due to SLMAP3 loss in these cells, although the expression of DVL3 was significantly reduced. Furthermore, MEFs lacking FGFR1OP2 or STRN3, two other STRIPAK members, did not reveal any significant changes in any of these parameters either. Significant changes in the number of ciliated cells and primary cilium length in SLMAP3 and FGFR1OP2 deficient MEFs were evident, while a reduced primary cilium length was notable in chondrocytes of SLMAP3 deficient embryos. Our findings suggest that SLMAP3 is essential for mouse embryogenesis through novel mechanisms involving the primary cilium/PCP and protein stability independent of Hippo signalling.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"rsob240206"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471741","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}

引用次数: 0

A cryptic plastid and a novel mitochondrial plasmid in Leucomyxa plasmidifera gen. and sp. nov. (Ochrophyta) push the frontiers of organellar biology. Leucomyxa plasmidifera gen.

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240022

Dovilė Barcytė, Karin Jaške, Tomáš Pánek, Tatiana Yurchenko, Tereza Ševčíková, Anežka Eliášová, Marek Eliáš

{"title":"A cryptic plastid and a novel mitochondrial plasmid in Leucomyxa plasmidifera gen. and sp. nov. (Ochrophyta) push the frontiers of organellar biology.","authors":"Dovilė Barcytė, Karin Jaške, Tomáš Pánek, Tatiana Yurchenko, Tereza Ševčíková, Anežka Eliášová, Marek Eliáš","doi":"10.1098/rsob.240022","DOIUrl":"10.1098/rsob.240022","url":null,"abstract":"Complete plastid loss seems to be very rare among secondarily non-photosynthetic eukaryotes. Leukarachnion sp. PRA-24, an amoeboid colourless protist related to the photosynthetic algal class Synchromophyceae (Ochrophyta), is a candidate for such a case based on a previous investigation by transmission electron microscopy. Here, we characterize this organism in further detail and describe it as Leucomyxa plasmidifera gen. et sp. nov., additionally demonstrating it is the first known representative of a broader clade of non-photosynthetic ochrophytes. We recovered its complete plastid genome, exhibiting a reduced gene set similar to plastomes of other non-photosynthetic ochrophytes, yet being even more extreme in sequence divergence. Identification of components of the plastid protein import machinery in the L. plasmidifera transcriptome assembly corroborated that the organism possesses a cryptic plastid organelle. According to our bioinformatic reconstruction, the plastid contains a unique combination of biosynthetic pathways producing haem, a folate precursor and tocotrienols. As another twist to its organellar biology, L. plasmidifera turned out to contain an unusual long insertion in its mitogenome related to a newly discovered mitochondrial plasmid exhibiting unprecedented features in terms of its size and coding capacity. Combined, our work uncovered further striking outcomes of the evolutionary course of semiautonomous organelles in protists.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240022"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546636","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}

引用次数: 0

Tail-anchored membrane protein SLMAP3 is essential for targeting centrosomal proteins to the nuclear envelope in skeletal myogenesis. 在骨骼肌发生过程中，尾锚膜蛋白SLMAP3对于将中心体蛋白靶向到核包膜至关重要。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240094

Ana Paula Dias, Taha Rehmani, Maysoon Salih, Balwant Tuana

{"title":"Tail-anchored membrane protein SLMAP3 is essential for targeting centrosomal proteins to the nuclear envelope in skeletal myogenesis.","authors":"Ana Paula Dias, Taha Rehmani, Maysoon Salih, Balwant Tuana","doi":"10.1098/rsob.240094","DOIUrl":"10.1098/rsob.240094","url":null,"abstract":"The positioning and communication between the nucleus and centrosomes are essential in cell division, differentiation and tissue formation. During skeletal myogenesis, the nuclei become evenly spaced with the switch of the microtubule-organizing centre (MTOC) from the centrosome to the nuclear envelope (NE). We report that the tail-anchored sarcolemmal membrane associated protein 3 (SLMAP3), a component of the MTOC and NE, is crucial for myogenesis because its deletion in mice leads to a reduction in the NE-MTOC formation, mislocalization of the nuclei, dysregulation of the myogenic programme and abnormal embryonic myofibres. SLMAP3-/- myoblasts also displayed a similar disorganized distribution of nuclei with an aberrant NE-MTOC and defective myofibre formation and differentiation programming. We identified novel interactors of SLMAP3, including pericentrin, PCM1 (pericentriolar material 1), AKAP9 (A-kinase anchoring protein 9), kinesin-1 members Kif5B (kinesin family member 5B), KCL1 (kinesin light chain 1), KLC2 (kinesin light chain 2) and nuclear lamins, and observed that the distribution of centrosomal proteins at the NE together with Nesprin-1 was significantly altered by the loss of SLMAP3 in differentiating myoblasts. SLMAP3 is believed to negatively regulate Hippo signalling, but its loss was without impact on this pathway in developing muscle. These results reveal that SLMAP3 is essential for skeletal myogenesis through unique mechanisms involving the positioning of nuclei, NE-MTOC dynamics and gene programming.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240094"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392241","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}

引用次数: 0

Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response. 斑马鱼揭示了 Fam83f 在孵化和 DNA 损伤介导的自噬反应中的新作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-23 DOI: 10.1098/rsob.240194

Rebecca A Jones, Fay Cooper, Gavin Kelly, David Barry, Matthew J Renshaw, Gopal Sapkota, James C Smith

{"title":"Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response.","authors":"Rebecca A Jones, Fay Cooper, Gavin Kelly, David Barry, Matthew J Renshaw, Gopal Sapkota, James C Smith","doi":"10.1098/rsob.240194","DOIUrl":"https://doi.org/10.1098/rsob.240194","url":null,"abstract":"The FAM83 (Family with sequence similarity 83) family is highly conserved in vertebrates, but little is known of the functions of these proteins beyond their association with oncogenesis. Of the family, FAM83F is of particular interest because it is the only membrane-targeted FAM83 protein. When overexpressed, FAM83F activates the canonical Wnt signalling pathway and binds to and stabilizes p53; it therefore interacts with two pathways often dysregulated in disease. Insights into gene function can often be gained by studying the roles they play during development, and here we report the generation of fam83f knock-out (KO) zebrafish, which we have used to study the role of Fam83f in vivo. We show that endogenous fam83f is most strongly expressed in the hatching gland of developing zebrafish embryos, and that fam83f KO embryos hatch earlier than their wild-type (WT) counterparts, despite developing at a comparable rate. We also demonstrate that fam83f KO embryos are more sensitive to ionizing radiation than WT embryos-an unexpected finding, bearing in mind the previously reported ability of FAM83F to stabilize p53. Transcriptomic analysis shows that loss of fam83f leads to downregulation of phosphatidylinositol-3-phosphate (PI(3)P) binding proteins and impairment of cellular degradation pathways, particularly autophagy, a crucial component of the DNA damage response. Finally, we show that Fam83f protein is itself targeted to the lysosome when overexpressed in HEK293T cells, and that this localization is dependent upon a C' terminal signal sequence. The zebrafish lines we have generated suggest that Fam83f plays an important role in autophagic/lysosomal processes, resulting in dysregulated hatching and increased sensitivity to genotoxic stress in vivo.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240194"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505306","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}

引用次数: 0

Haploidy-linked cell proliferation defects limit larval growth in zebrafish. 与单倍体相关的细胞增殖缺陷限制了斑马鱼幼体的生长。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240126

Kan Yaguchi, Daiki Saito, Triveni Menon, Akira Matsura, Miyu Hosono, Takeomi Mizutani, Tomoya Kotani, Sreelaja Nair, Ryota Uehara

{"title":"Haploidy-linked cell proliferation defects limit larval growth in zebrafish.","authors":"Kan Yaguchi, Daiki Saito, Triveni Menon, Akira Matsura, Miyu Hosono, Takeomi Mizutani, Tomoya Kotani, Sreelaja Nair, Ryota Uehara","doi":"10.1098/rsob.240126","DOIUrl":"10.1098/rsob.240126","url":null,"abstract":"Haploid larvae in non-mammalian vertebrates are lethal, with characteristic organ growth retardation collectively called 'haploid syndrome'. In contrast to mammals, whose haploid intolerance is attributed to imprinting misregulation, the cellular principle of haploidy-linked defects in non-mammalian vertebrates remains unknown. Here, we investigated cellular defects that disrupt the ontogeny of gynogenetic haploid zebrafish larvae. Unlike diploid control larvae, haploid larvae manifested unscheduled cell death at the organogenesis stage, attributed to haploidy-linked p53 upregulation. Moreover, we found that haploid larvae specifically suffered the gradual aggravation of mitotic spindle monopolarization during 1-3 days post-fertilization, causing spindle assembly checkpoint-mediated mitotic arrest throughout the entire body. High-resolution imaging revealed that this mitotic defect accompanied the haploidy-linked centrosome loss occurring concomitantly with the gradual decrease in larval cell size. Either resolution of mitotic arrest or depletion of p53 partially improved organ growth in haploid larvae. Based on these results, we propose that haploidy-linked mitotic defects and cell death are parts of critical cellular causes shared among vertebrates that limit the larval growth in the haploid state, contributing to an evolutionary constraint on allowable ploidy status in the vertebrate life cycle.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240126"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392240","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}

引用次数: 0