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Melastatin subfamily Transient Receptor Potential channels support spermatogenesis in planarian flatworms. Melastatin 亚家族瞬时受体电位通道支持扁虫的精子发生。
bioRxiv - Developmental Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.01.610670
Haley Nicole Curry, Roger Huynh, Labib Rouhana
{"title":"Melastatin subfamily Transient Receptor Potential channels support spermatogenesis in planarian flatworms.","authors":"Haley Nicole Curry, Roger Huynh, Labib Rouhana","doi":"10.1101/2024.09.01.610670","DOIUrl":"https://doi.org/10.1101/2024.09.01.610670","url":null,"abstract":"The Transient Receptor Potential superfamily of proteins (TRPs) form cation channels that are abundant in animal sensory systems. Amongst TRPs, the Melastatin-related subfamily (TRPMs) is composed of members that respond to temperature, pH, sex hormones, and various other stimuli. Some TRPMs exhibit enriched expression in gonads of vertebrate and invertebrate species, but their contributions to germline development remain to be determined. We identified twenty-one potential TRPMs in the planarian flatworm Schmidtea mediterranea and analyzed their anatomical distribution of expression by whole-mount in situ hybridization. Enriched expression of two TRPMs (Smed-TRPM-c and Smed-TRPM-l) was detected in testis, whereas eight TRPM genes had detectable expression in patterns representative of neuronal and/or sensory cell types. Functional analysis of TRPM homologs by RNA-interference (RNAi) revealed that disruption of Smed-TRPM-c expression results in reduced sperm development, indicating a role for this receptor in supporting spermatogenesis. Smed-TRPM-l RNAi did not result in a detectable phenotype, but it increased sperm development deficiencies when combined with Smed-TRPM-c RNAi. Fluorescence in situ hybridization revealed expression of Smed-TRPM-c in early spermatogenic cells within testes, suggesting cell-autonomous regulatory functions in germ cells for this gene. In addition, Smed-TRPM-c RNAi resulted in reduced numbers of presumptive germline stem cell clusters in asexual planarians, suggesting that Smed-TRPM-c supports establishment, maintenance, and/or expansion of spermatogonial germline stem cells. While further research is needed to identify the factors that trigger Smed-TRPM-c activity, these findings reveal one of few known examples for TRPM function in direct regulation of sperm development.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
​​The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells miR-290 和 miR-302 簇对成纤维细胞重编程为诱导多能干细胞至关重要
bioRxiv - Developmental Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.02.610895
Julia Ye, Ryan M Boileau, Ronald J Parchem, Robert L Judson-Torres, Robert Blelloch
{"title":"​​The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells","authors":"Julia Ye, Ryan M Boileau, Ronald J Parchem, Robert L Judson-Torres, Robert Blelloch","doi":"10.1101/2024.09.02.610895","DOIUrl":"https://doi.org/10.1101/2024.09.02.610895","url":null,"abstract":"The miR-290 and miR-302 clusters of microRNAs are highly expressed in naive and primed pluripotent stem cells, respectively. Ectopic expression of the embryonic stem cell-specific cell cycle regulating (ESCC) family of microRNAs arising from these two clusters dramatically enhances the reprogramming of both mouse and human somatic cells to induced pluripotency. Here, we used genetic knockouts to dissect the requirement for the miR-290 and miR-302 clusters during the reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs) with retrovirally introduced Oct4, Sox2, and Klf4. Knockout of either cluster alone did not negatively impact the efficiency of reprogramming. Resulting cells appeared identical to their embryonic stem cell microRNA cluster knockout counterparts. In contrast, the combined loss of both clusters blocked the formation of iPSCs. While rare double knockout clones could be isolated, they showed a dramatically reduced proliferation rate, a persistent inability to fully silence the exogenously introduced pluripotency factors, and a transcriptome distinct from individual miR-290 or miR-302 mutant ESC and iPSCs. Taken together, our data show that miR-290 and miR-302 are essential yet interchangeable in reprogramming to the induced pluripotent state.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wnt5a and Notum Influence the Temporal Dynamics of Cartilaginous Mesenchymal Condensations in Developing Trachea. Wnt5a和Notum影响发育中气管软骨间充质凝集的时间动态
bioRxiv - Developmental Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.09.02.610014
Natalia Bottasso-Arias, Megha Mohanakrishnan, Sarah Trovillion, Kaulini Burra, Nicholas Russell, Yixin Wu, Yan Xu, Debora I Sinner
{"title":"Wnt5a and Notum Influence the Temporal Dynamics of Cartilaginous Mesenchymal Condensations in Developing Trachea.","authors":"Natalia Bottasso-Arias, Megha Mohanakrishnan, Sarah Trovillion, Kaulini Burra, Nicholas Russell, Yixin Wu, Yan Xu, Debora I Sinner","doi":"10.1101/2024.09.02.610014","DOIUrl":"https://doi.org/10.1101/2024.09.02.610014","url":null,"abstract":"The trachea is essential for proper airflow to the lungs for gas exchange. Frequent congenital tracheal malformations affect the cartilage, causing the collapse of the central airway during the respiratory cycle. We have shown that Notum, a Wnt ligand de-acylase that attenuates the canonical branch of the Wnt signaling pathway, is necessary for cartilaginous mesenchymal condensations. In Notum deficient tracheas, chondrogenesis is delayed, and the tracheal lumen is narrowed. It is unknown if Notum attenuates non-canonical Wnt signaling. Notably, we observed premature tracheal chondrogenesis after mesenchymal deletion of the non-canonical Wnt5a ligand. We hypothesize that Notum and Wnt5a are required to mediate the timely formation of mesenchymal condensations, giving rise to the tracheal cartilage. Ex vivo culture of tracheal tissue shows that chemical inhibition of the Wnt non-canonical pathway promotes earlier condensations, while Notum inhibition presents delayed condensations. Furthermore, non-canonical Wnt induction prevents the formation of cartilaginous mesenchymal condensations. On the other hand, cell-cell interactions among chondroblasts increase in the absence of mesenchymal Wnt5a. By performing an unbiased analysis of the gene expression in Wnt5a and Notum deficient tracheas, we detect that mRNA of genes essential for chondrogenesis and extracellular matrix formation are upregulated by E11.5 in Wnt5a mutants. The expression profile supports the premature and delayed chondrogenesis observed in Wnt5a and Notum deficient tracheas, respectively. We conclude that Notum and Wnt5a are necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis. Thus, these studies shed light on molecular mechanisms underlying congenital anomalies of the trachea.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developmental Effects of Lithium and Zinc in Planaria 锂和锌对扁虱发育的影响
bioRxiv - Developmental Biology Pub Date : 2024-09-03 DOI: 10.1101/2024.08.30.610554
Alberto Molano
{"title":"Developmental Effects of Lithium and Zinc in Planaria","authors":"Alberto Molano","doi":"10.1101/2024.08.30.610554","DOIUrl":"https://doi.org/10.1101/2024.08.30.610554","url":null,"abstract":"An investigation was carried out of the stage-specific effects of lithium and zinc on planaria embryologic development. These two reagents had dramatically different effects on the morphological development of planaria: Zinc induced the formation of bifurcations or trifurcations of the head region. In contrast, lithium induced the formation of round masses of cells. The earliest embryological stages (S1 and S2, cryptic larva formation) exhibited extreme sensitivity to lithium, since the lethal dose was at least one order of magnitude lower than for subsequent stages 3-5, suggesting that beta-catenin 1 expression is tightly regulated during the initial embryologic stages and that even slightly increased activity is lethal.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultra-low photodamage three-photon microscopy assisted by neural network for monitoring regenerative myogenesis 神经网络辅助超低光损伤三光子显微镜监测再生肌生成
bioRxiv - Developmental Biology Pub Date : 2024-08-11 DOI: 10.1101/2024.08.11.607469
Yifei Li, keying Li, Mubin He, Chenlin Liang, Xin Xie, Jun Qian
{"title":"Ultra-low photodamage three-photon microscopy assisted by neural network for monitoring regenerative myogenesis","authors":"Yifei Li, keying Li, Mubin He, Chenlin Liang, Xin Xie, Jun Qian","doi":"10.1101/2024.08.11.607469","DOIUrl":"https://doi.org/10.1101/2024.08.11.607469","url":null,"abstract":"Three-photon microscopy (3PM) enables high-resolution three-dimensional (3D) imaging in deeply situated and highly scattering biological specimens, facilitating precise characterization of biological morphology and cellular-level physiology in vivo. However, the use of fluorescent probes with relatively low three-photon absorption cross-sections necessitates high-peak-power lasers for excitation, which poses inherent risks of light-induced damage. Additionally, the low repetition frequency of these lasers prolongs scanning time per pixel, hampering imaging speed and exacerbating the potential for photodamage. Such limitations hinder the application of 3PM in studying vulnerable tissues, including muscle regeneration. To address this critical issue, we developed the Multi-Scale Attention Denoising Network (MSAD-Net), a precise and versatile denoising network suitable for diverse structures and varying noise levels. Our network enables the use of lower excitation power (1/4-1/2 of the common power) and shorter scanning time (1/6-1/4 of the common time) in 3PM while preserving image quality and tissue integrity. It achieves an impressive structural similarity index (SSIM) of up to 0.9932 and an incredibly fast inference time of just 80 milliseconds per frame which ensured both high fidelity and practicality for downstream applications. By utilizing MSAD-Net-assisted imaging, we comprehensively characterize the biological morphology and functionality of muscle regeneration processes through deep in vivo five-channel imaging under extremely low excitation power and short scanning time, while maintaining a high signal-to-background ratio (SBR) and excellent axial spatial resolution. Furthermore, we conducted high axial-resolution dynamic imaging of vascular microcirculation, macrophages, and ghost fibers. Our findings provide a deeper understanding of the mechanisms underlying muscle regeneration at the cellular and tissue levels.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic Wt1 expression in the gastrulation-stage mouse embryo specifies vascular and visceral smooth muscle cell fate independently from mesothelial fate. 小鼠胚胎中 Wt1 的动态表达决定了血管和内脏平滑肌细胞的命运,而与间皮细胞的命运无关。
bioRxiv - Developmental Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.08.607207
Suad Hassan Alsukari, Huei Teng Ng, Lilly Lang, Sharna Lunn, Shanthi Beglinger, Lauren Carr, Michael Boyes, David Andrew Turner, Bettina Wilm
{"title":"Dynamic Wt1 expression in the gastrulation-stage mouse embryo specifies vascular and visceral smooth muscle cell fate independently from mesothelial fate.","authors":"Suad Hassan Alsukari, Huei Teng Ng, Lilly Lang, Sharna Lunn, Shanthi Beglinger, Lauren Carr, Michael Boyes, David Andrew Turner, Bettina Wilm","doi":"10.1101/2024.08.08.607207","DOIUrl":"https://doi.org/10.1101/2024.08.08.607207","url":null,"abstract":"The Wilms' Tumour protein (Wt1) had previously been shown to specify both the mesothelial lineage and vascular smooth muscle cell (vSMC) lineage in the mouse intestine, with evidence suggesting that intestinal vSMCs arise from the mesothelium. Here, we dissect the temporal relationship between these two mesodermal lineages, reporting that unexpectedly, Wt1 expression already in gastrulation stage embryos specifies a population of SMC precursor cells in the lateral plate mesoderm (LPM). Tamoxifen-induced genetic lineage tracing of Wt1-expressing cells revealed that vSMC and visceral smooth muscle cells (viSMCs) of the foetal mid-gut are labelled when Tamoxifen was administered at E7.5 or E8.5. By contrast, intestinal mesothelial cells were labelled after Tamoxifen dosing from E9.5 and later. Analysis of scRNAseq data of gastrulation stage mouse embryos and confocal microscopy demonstrated for the first time Wt1 expression in epiblast and primitive streak, emerging mesoderm and, from E7.5 onwards, in the LPM. In E8.5 mouse embryos, the co-expression of key smooth muscle fate markers Tagln, Acta2, MrtfA/B and Pdgfrb in Wt1-expressing cells revealed that vSMC and viSMC fate is specified independently from visceral mesothelium formation. Together, our study provides insight into the developmental lineage of smooth muscle specified by Wt1 expression at gastrulation stages.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A sperm-enriched 5'fragment of tRNA-Valine regulates preimplantation embryonic transcriptome and development 富含精子的 tRNA-Valine 5'片段调控植入前胚胎转录组和发育
bioRxiv - Developmental Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.08.607197
Simeiyun Liu, Andrew D Holmes, Sol Katzman, Upasna Sharma
{"title":"A sperm-enriched 5'fragment of tRNA-Valine regulates preimplantation embryonic transcriptome and development","authors":"Simeiyun Liu, Andrew D Holmes, Sol Katzman, Upasna Sharma","doi":"10.1101/2024.08.08.607197","DOIUrl":"https://doi.org/10.1101/2024.08.08.607197","url":null,"abstract":"Sperm small RNAs have been implicated in intergenerational epigenetic inheritance of paternal environmental effects; however, their biogenesis and functions remain poorly understood. We previously identified a 5' fragment of tRNA-Valine-CAC-2 (tRFValCAC) as one of the most abundant small RNA in mature sperm. tRFValCAC is specifically enriched in sperm during post-testicular maturation in the epididymis, and we found that it is delivered to sperm from epididymis epithelial cells via extracellular vesicles. Here, we investigated the mechanistic basis of tRFValCAC delivery to sperm and its functions in the early embryo. We show that tRFValCAC interacts with an RNA binding protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB), in the epididymis, and this interaction regulates the sorting and packing of tRFValCAC into extracellular vesicles. In the embryo, we found that tRFValCAC regulates early embryonic mRNA processing and splicing. Inhibition of tRFValCAC in preimplantation embryos altered the transcript abundance of genes involved in RNA splicing and mRNA processing. Importantly, tRFValCAC-inhibited embryos showed altered mRNA splicing, including alternative splicing of various splicing factors and genes important for proper preimplantation embryonic development. Finally, we find that inhibition of tRFValCAC in zygotes delayed preimplantation embryonic development. Together, our results reveal a novel function of a sperm-enriched tRF in regulating alternating splicing and preimplantation embryonic development and shed light on the mechanism of sperm small RNA-mediated epigenetic inheritance.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Material Properties Of The Embryonic Small Intestine During Buckling Morphogenesis 胚胎小肠弯曲变形过程中的材料特性
bioRxiv - Developmental Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.07.606927
Jenny Gao, Lucia Grace Martin, Elise A Loffet, John Francis Durel, Panagiotis Oikonomou, Nandan Nerurkar
{"title":"Material Properties Of The Embryonic Small Intestine During Buckling Morphogenesis","authors":"Jenny Gao, Lucia Grace Martin, Elise A Loffet, John Francis Durel, Panagiotis Oikonomou, Nandan Nerurkar","doi":"10.1101/2024.08.07.606927","DOIUrl":"https://doi.org/10.1101/2024.08.07.606927","url":null,"abstract":"During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops with wavelength and curvature that are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypoxia promotes airway differentiation in the human lung epithelium 缺氧促进人类肺上皮细胞的气道分化
bioRxiv - Developmental Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.09.607336
Ziqi Dong, Niek Wit, Aastha Agarwal, Dnyanesh Dubal, Jelle van den Ameele, Adam James Reid, James A Nathan, Emma Rawlins
{"title":"Hypoxia promotes airway differentiation in the human lung epithelium","authors":"Ziqi Dong, Niek Wit, Aastha Agarwal, Dnyanesh Dubal, Jelle van den Ameele, Adam James Reid, James A Nathan, Emma Rawlins","doi":"10.1101/2024.08.09.607336","DOIUrl":"https://doi.org/10.1101/2024.08.09.607336","url":null,"abstract":"Human early embryos develop under physiological hypoxia, but how hypoxia regulates human organogenesis remains little known. We have investigated oxygen availability effects on the human lung epithelium using organoids. We find first-trimester lung epithelial progenitors remain undifferentiated under normoxia, but spontaneously differentiate towards multiple airway cell types and inhibit alveolar differentiation under hypoxia. Using chemical and genetic tools, we demonstrate that hypoxia-induced airway differentiation is dependent on HIF (Hypoxia-Inducible Factor) pathways, with HIF1α and HIF2α differentially regulating fate decisions. Transcription factors KLF4 and KLF5 are direct targets of the HIF pathway and promote progenitor differentiation to basal and secretory cells. Chronic hypoxia also induces transdifferentiation of human alveolar type 2 cells to airway cells via the HIF pathway, mimicking alveolar bronchiolization processes in lung disease. Our results reveal roles for hypoxia and HIF signalling during human lung development and have implications for aberrant cell fate decisions in chronic lung diseases.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hippo-TOR Signaling Crosstalks Underpin Microtubule Acetylation-linked Carcinogenesis in Drosophila Squamous Epithelia 果蝇鳞状上皮细胞中与微管乙酰化相关的致癌作用的基础是Hippo-TOR信号交叉
bioRxiv - Developmental Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.08.607173
Rachita Bhattacharya, PRADIP SINHA, Nitin Mohan
{"title":"Hippo-TOR Signaling Crosstalks Underpin Microtubule Acetylation-linked Carcinogenesis in Drosophila Squamous Epithelia","authors":"Rachita Bhattacharya, PRADIP SINHA, Nitin Mohan","doi":"10.1101/2024.08.08.607173","DOIUrl":"https://doi.org/10.1101/2024.08.08.607173","url":null,"abstract":"Post-translational modifications (PTM), like acetylation, underpin the functional specialization of the cytoskeleton, such as microtubules (MT). For instance, acetylation of microbules is essential for cell flattening in the Drosophila adult squamous epithelia of female ovarian follicles and male accessory glands (MAG). Here we show that the highly conserved Hippo transcription co-factor Yorkie (Yki), a mechanosensor for cell flattening, regulates the acetylation of MT in squamous epithelia in both these organs. Yet, the fallouts of loss of nuclear Yki signaling are distinct in these two squamous epithelia. Thus, the knockdown of Yki in the squamous epithelia of ovarian follicles compromises their cell flattening. By contrast, knockdown of Yki in the MAG epithelium leads to its cancerous transformation which is suppressed by a simultaneous genetic ablation of MT-acetylation. We further note that Yki-knockdown-induced hyperacetylation of MT in MAG is TOR signaling-dependent. These results reveal that, while Yki-dependent acetylation of MT drives cell flattening, its cell type-specific homeostatic cross-talk with TOR signaling, as in the MAG, when dysregulated, culminates in carcinogenesis.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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