genesis最新文献

{"title":"Generation and Characterization of a TRIM21 Overexpressing Mouse Line","authors":"Lisa M. Mehlmann,&nbsp;Tracy F. Uliasz,&nbsp;Siu-Pok Yee,&nbsp;Deborah Kaback,&nbsp;Katie M. Lowther","doi":"10.1002/dvg.23616","DOIUrl":"10.1002/dvg.23616","url":null,"abstract":"<p>Specific removal of a protein is a key to understanding its function. “Trim-Away” utilizes TRIM21, an antibody receptor and ubiquitin ligase, for acute and specific reduction of proteins. When TRIM21 is expressed in cells, introduction of a specific antibody causes rapid degradation of the targeted protein; however, TRIM21 is endogenously expressed in few cell types. We have generated a mouse line using CRISPR to insert a conditional overexpression cassette of TRIM21 into the safe harbor site, <i>Rosa26</i>. These conditionally-expressing mice can be bred to a wide variety of <i>Cre</i> mice to target cell-specific TRIM21 overexpression in different tissues. <i>Zp3</i>^<i>Cre</i> mice expressed TRIM21 protein specifically in oocytes, whereas <i>Hprt</i>^<i>Cre</i> mice expressed the protein globally. When TRIM21-overexpressing oocytes were microinjected with specific antibodies targeting either the IP₃ receptor or SNAP23, these proteins were effectively degraded. In addition, cortical neural cells from globally-overexpressing TRIM21 mice showed a dramatic reduction in IP₃ receptor protein within hours after electroporation of a specific antibody. These experiments confirm the effectiveness of the Trim-Away method for protein reduction. These mice should make a valuable addition to the broader research community, as a wide range of proteins and cell types can be studied using this method.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.23616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and Transcriptional Targets of TGFβ-RII in Paracentrotus lividus Larval Skeletogenesis","authors":"Daniel Goloe,&nbsp;Tsvia Gildor,&nbsp;Smadar Ben-Tabou de-Leon","doi":"10.1002/dvg.23614","DOIUrl":"10.1002/dvg.23614","url":null,"abstract":"<p>Organisms from the five kingdoms of life use minerals to harden their tissues and make teeth, shells and skeletons, in the process of biomineralization. The sea urchin larval skeleton is an excellent system to study the biological regulation of biomineralization and its evolution. The gene regulatory network (GRN) that controls sea urchin skeletogenesis is known in great details and shows similarity to the GRN that controls vertebrates' vascularization while it is quite distinct from the GRN that drives vertebrates' bone formation. Yet, transforming growth factor beta (TGF-β) signaling regulates both sea urchin and vertebrates' skeletogenesis. Here, we study the upstream regulation and identify transcriptional targets of TGF-β in the Mediterranean Sea urchin species, <i>Paracentrotus lividus.</i> TGF-βRII is transiently active in the skeletogenic cells downstream of vascular endothelial growth factor (VEGF) signaling, in <i>P. lividus</i>. Continuous perturbation of TGF-βRII activity significantly impairs skeletal elongation and the expression of key skeletogenic genes. Perturbation of TGF-βRII after skeletal initiation leads to a delay in skeletal elongation and minor changes in gene expression. TGF-β targets are distinct from its transcriptional targets during vertebrates' bone formation, suggesting that the role of TGF-β in biomineralization in these two phyla results from convergent evolution.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.23614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of an Armcx1 Conditional Knockout Mouse","authors":"Cora L. Bright,&nbsp;Howard M. Bomze,&nbsp;Mantu Bhaumik,&nbsp;Jeremy N. Kay,&nbsp;Romain Cartoni,&nbsp;Sidney M. Gospe III","doi":"10.1002/dvg.23615","DOIUrl":"10.1002/dvg.23615","url":null,"abstract":"<div>\u0000 \u0000 <p>Armadillo repeat-containing X-linked protein-1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 <i>in vivo</i>, we have created a conditional <i>Armcx1</i> knockout mouse line in which the entire coding region of the <i>Armcx1</i> gene is flanked by <i>loxP</i> sites. This <i>Armcx1</i>^<i>fl</i> line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for <i>β-actin</i> and <i>Six3</i>, in order to achieve deletion of <i>Armcx1</i> globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in <i>Armcx1</i> knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The <i>Armcx1</i>^<i>fl</i> mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1-deficient neurons to degeneration in the setting of additional heritable or environmental stressors.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sox21 homeologs autoregulate expression levels to control progression through neurogenesis","authors":"Dillon L. Damuth,&nbsp;Doreen D. Cunningham,&nbsp;Elena M. Silva","doi":"10.1002/dvg.23612","DOIUrl":"10.1002/dvg.23612","url":null,"abstract":"<div>\u0000 \u0000 <p>The SRY HMG box transcription factor Sox21 plays multiple critical roles in neurogenesis, with its function dependent on concentration and developmental stage. In the allotetraploid <i>Xenopus laevis</i>, there are two homeologs of <i>sox21</i>, namely <i>sox21.S</i> and <i>sox21.L</i>. Previous studies focused on Sox21.S, but its amino acid sequence is divergent, lacking conserved poly-A stretches and bearing more similarity with ancestral homologs. In contrast, Sox21.L shares higher sequence similarity with mouse and chick Sox21. To determine if Sox21.S and Sox21.L have distinct functions, we conducted gain and loss-of-function studies in <i>Xenopus</i> embryos. Our studies revealed that Sox21.S and Sox21.L are functionally redundant, but Sox21.L is more effective at driving changes than Sox21.S. These results also support our earlier findings in ectodermal explants, demonstrating that Sox21 function is dose-dependent. While Sox21 is necessary for primary neuron formation, high levels prevent their formation. Strikingly, these proteins autoregulate, with high levels of Sox21.L reducing <i>sox21.S</i> and <i>sox21.L</i> mRNA levels, and decreased Sox21.S promoting increased expression of <i>sox21.L</i>. Our findings shed light on the intricate concentration-dependent roles of Sox21 homeologs in <i>Xenopus</i> neurogenesis.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two decades on: Special issue on olfaction celebrating Axel and Buck's Nobel Prize","authors":"Paolo E. Forni,&nbsp;C. Ron Yu","doi":"10.1002/dvg.23613","DOIUrl":"10.1002/dvg.23613","url":null,"abstract":"","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of olfactory experience on the birthrates of olfactory sensory neurons with specific odorant receptor identities","authors":"Karlin E. Rufenacht,&nbsp;Alexa J. Asson,&nbsp;Kawsar Hossain,&nbsp;Stephen W. Santoro","doi":"10.1002/dvg.23611","DOIUrl":"10.1002/dvg.23611","url":null,"abstract":"<div>\u0000 \u0000 <p>Olfactory sensory neurons (OSNs) are one of a few neuron types that are generated continuously throughout life in mammals. The persistence of olfactory sensory neurogenesis beyond early development has long been thought to function simply to replace neurons that are lost or damaged through exposure to environmental insults. The possibility that olfactory sensory neurogenesis may also serve an adaptive function has received relatively little consideration, largely due to the assumption that the generation of new OSNs is stochastic with respect to OSN subtype, as defined by the single odorant receptor gene that each neural precursor stochastically chooses for expression out of hundreds of possibilities. Accordingly, the relative birthrates of different OSN subtypes are predicted to be constant and impervious to olfactory experience. This assumption has been called into question, however, by evidence that the birthrates of specific OSN subtypes can be selectively altered by manipulating olfactory experience through olfactory deprivation, enrichment, and conditioning paradigms. Moreover, studies of recovery of the OSN population following injury provide further evidence that olfactory sensory neurogenesis may not be strictly stochastic with respect to subtype. Here we review this evidence and consider mechanistic and functional implications of the prospect that specific olfactory experiences can regulate olfactory sensory neurogenesis rates in a subtype-selective manner.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of odorant receptors during olfactory glomerular map formation","authors":"Ai Nakashima,&nbsp;Haruki Takeuchi","doi":"10.1002/dvg.23610","DOIUrl":"10.1002/dvg.23610","url":null,"abstract":"<p>The organization of the olfactory glomerular map involves the convergence of olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) into glomeruli in the olfactory bulb (OB). A remarkable feature of the olfactory glomerular map formation is that the identity of OR instructs the topography of the bulb, resulting in thousands of discrete glomeruli in mice. Several lines of evidence indicate that ORs control the expression levels of various kinds of transmembrane proteins to form glomeruli at appropriate regions of the OB. In this review, we will discuss how the OR identity is decoded by OSNs into gene expression through intracellular regulatory mechanisms.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.23610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSCNN1A inhibits the proliferation, migration and invasion of renal cell carcinoma cells by decreasing CLDN8 expression through miR-590-5p","authors":"Tingting Guo,&nbsp;Wanjuan Xiong,&nbsp;Chong Liu,&nbsp;Li Zhu,&nbsp;Ling Xie","doi":"10.1002/dvg.23599","DOIUrl":"10.1002/dvg.23599","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Increasing evidence suggests that circular RNA (circRNA) plays a regulatory role in the progression of renal cell carcinoma (RCC). However, the precise function and underlying mechanism of circSCNN1A in RCC progression still remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression levels of circSCNN1A, microRNA-590-5p (miR-590-5p), claudin 8 (CLDN8), cyclin D1, matrix metalloprotein 2 (MMP2), MMP9, E-cadherin, N-cadherin and vimentin were detected by a quantitative real-time polymerase chain reaction and Western blotting analysis. Immunohistochemistry assay was performed to analyze the positive expression rate of CLDN8. Cell proliferation was investigated by cell colony formation, 5-Ethynyl-2′-deoxyuridine and DNA content quantitation assays. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Interactions among circSCNN1A, miR-590-5p and CLDN8 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft mouse model assay was conducted to verify the effect of circSCNN1A on tumor formation in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CircSCNN1A and CLDN8 expression were significantly downregulated, while miR-590-5p was upregulated in both RCC tissues and cells. CircSCNN1A overexpression inhibited RCC cell proliferation, migration and invasion, accompanied by decreases of cyclin D1, MMP2, MMP9, N-cadherin and vimentin expression and an increase of E-cadherin expression. CircSCNN1A acted as a miR-590-5p sponge and regulated RCC cell processes by binding to miR-590-5p. CLDN8, a target gene of miR-590-5p, was involved in the regulation of the biological behaviors of RCC cells by miR-590-5p. In addition, circSCNN1A induced CLDN8 production by interacting with miR-590-5p. Further, circSCNN1A suppressed tumor formation in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CircSCNN1A inhibited RCC cell proliferation, migration and invasion by regulating the miR-590-5p/CLDN8 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphodiesterase 5A regulates the vomeronasal pump in mice","authors":"Dennean S. Lippner,&nbsp;Jiang Xu,&nbsp;Siqi Ma,&nbsp;Johannes Reisert,&nbsp;Haiqing Zhao","doi":"10.1002/dvg.23603","DOIUrl":"10.1002/dvg.23603","url":null,"abstract":"<div>\u0000 \u0000 <p>The vomeronasal organ (VNO) is a specialized chemoreceptive structure in many vertebrates that detects chemical stimuli, mostly pheromones, which often elicit innate behaviors such as mating and aggression. Previous studies in rodents have demonstrated that chemical stimuli are actively transported to the VNO via a blood vessel-based pumping mechanism, and this pumping mechanism is necessary for vomeronasal stimulation in behaving animals. However, the molecular mechanisms that regulate the vomeronasal pump remain mostly unknown. In this study, we observed a high level of expression of phosphodiesterase 5A (PDE5A) in the vomeronasal blood vessel of mice. We provided evidence to support the potential role of PDE5A in vomeronasal pump regulation. Local application of PDE5A inhibitors—sildenafil or tadalafil—to the vomeronasal organ (VNO) reduced stimulus delivery into the VNO, decreased the pheromone-induced activity of vomeronasal sensory neurons, and attenuated male–male aggressive behaviors. PDE5A is well known to play a role in regulating blood vessel tone in several organs. Our study advances our understanding of the molecular regulation of the vomeronasal pump.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas9 delivery strategies and applications: Review and update","authors":"Ali Alizadeh Severi,&nbsp;Bahman Akbari","doi":"10.1002/dvg.23598","DOIUrl":"10.1002/dvg.23598","url":null,"abstract":"<div>\u0000 \u0000 <p>Nowadays, a significant part of the investigations carried out in the medical field belong to cancer treatment. Generally, conventional cancer treatments, including chemotherapy, radiotherapy, and surgery, which have been used for a long time, are not sufficient, especially in malignant cancers. Because genetic mutations cause cancers, researchers are trying to treat these diseases using genetic engineering tools. One of them is clustered regularly interspaced short palindromic repeats (CRISPR), a powerful tool in genetic engineering in the last decade. CRISPR, which forms the CRISPR-Cas structure with its endonuclease protein, Cas, is known as a part of the immune system (adaptive immunity) in bacteria and archaea. Among the types of Cas proteins, Cas9 endonuclease has been used in many scientific studies due to its high accuracy and efficiency. This review reviews the CRISPR system, focusing on the history, classification, delivery methods, applications, new generations, and challenges of CRISPR-Cas9 technology.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}