Journal of Developmental Biology最新文献

{"title":"Genetic and Epigenetic Regulation of <i>Drosophila</i> Oocyte Determination.","authors":"Brigite Cabrita,&nbsp;Rui Gonçalo Martinho","doi":"10.3390/jdb11020021","DOIUrl":"https://doi.org/10.3390/jdb11020021","url":null,"abstract":"<p><p>Primary oocyte determination occurs in many organisms within a germ line cyst, a multicellular structure composed of interconnected germ cells. However, the structure of the cyst is itself highly diverse, which raises intriguing questions about the benefits of this stereotypical multicellular environment for female gametogenesis. <i>Drosophila melanogaster</i> is a well-studied model for female gametogenesis, and numerous genes and pathways critical for the determination and differentiation of a viable female gamete have been identified. This review provides an up-to-date overview of <i>Drosophila</i> oocyte determination, with a particular emphasis on the mechanisms that regulate germ line gene expression.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of Dopaminergic Neurodegeneration in a <i>C. elegans</i> Parkinson's Model through Regulation of Xanthine Dehydrogenase (XDH-1) Expression by the RNA Editase, ADR-2.","authors":"Lindsey A Starr,&nbsp;Luke E McKay,&nbsp;Kylie N Peter,&nbsp;Lena M Seyfarth,&nbsp;Laura A Berkowitz,&nbsp;Kim A Caldwell,&nbsp;Guy A Caldwell","doi":"10.3390/jdb11020020","DOIUrl":"https://doi.org/10.3390/jdb11020020","url":null,"abstract":"<p><p>Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicated in several neurological disorders, including Parkinson's disease (PD). Here, we report results of a RNAi screen of genes differentially regulated in <i>adr-2</i> mutants, normally encoding the only catalytically active ADAR in <i>Caenorhabditis elegans</i>, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegeneration, two PD pathologies, reveal that reduced expression of <i>xdh-1</i>, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegeneration. Further, RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. In silico structural modeling of WHT-2 indicates that the editing of one nucleotide in the <i>wht-2</i> mRNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing hydrogen bonds in this region. Thus, we propose a model where <i>wht-2</i> is edited by ADR-2, which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited, provoking a reduction in <i>xdh-1</i> transcription to limit uric acid production and maintain cellular homeostasis. As a result, elevation of uric acid is protective against dopaminergic neuronal cell death. In turn, increased levels of uric acid are associated with a decrease in ROS production. Further, downregulation of <i>xdh-1</i> is protective against PD pathologies because decreased levels of XDH-1 correlate to a concomitant reduction in xanthine oxidase (XO), the form of the protein whose by-product is superoxide anion. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Presence of Two <i>MyoD</i> Genes in a Subset of Acanthopterygii Fish Is Associated with a Polyserine Insert in MyoD1.","authors":"Lewis J White,&nbsp;Alexander J Russell,&nbsp;Alastair R Pizzey,&nbsp;Kanchon K Dasmahapatra,&nbsp;Mary E Pownall","doi":"10.3390/jdb11020019","DOIUrl":"https://doi.org/10.3390/jdb11020019","url":null,"abstract":"<p><p>The <i>MyoD</i> gene was duplicated during the teleost whole genome duplication and, while a second <i>MyoD</i> gene (<i>MyoD2</i>) was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including <i>Alcolapia</i> species) have retained both <i>MyoD</i> paralogues. Here we reveal the expression patterns of the two <i>MyoD</i> genes in <i>Oreochromis</i> (<i>Alcolapia) alcalica</i> using in situ hybridisation. We report our analysis of MyoD1 and MyoD2 protein sequences from 54 teleost species, and show that <i>O. alcalica</i>, along with some other teleosts, include a polyserine repeat between the amino terminal transactivation domains (TAD) and the cysteine-histidine rich region (H/C) in MyoD1. The evolutionary history of <i>MyoD1</i> and <i>MyoD2</i> is compared to the presence of this polyserine region using phylogenetics, and its functional relevance is tested using overexpression in a heterologous system to investigate subcellular localisation, stability, and activity of MyoD proteins that include and do not include the polyserine region.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9508967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive-Toxicity-Related Endpoints in <i>C. elegans</i> Are Consistent with Reduced Concern for Dimethylarsinic Acid Exposure Relative to Inorganic Arsenic.","authors":"Jessica A Camacho, Bonnie Welch, Robert L Sprando, Piper R Hunt","doi":"10.3390/jdb11020018","DOIUrl":"10.3390/jdb11020018","url":null,"abstract":"<p><p>Exposures to arsenic and mercury are known to pose significant threats to human health; however, the effects specific to organic vs. inorganic forms are not fully understood. <i>Caenorhabditis elegans'</i> (<i>C. elegans</i>) transparent cuticle, along with the conservation of key genetic pathways regulating developmental and reproductive toxicology (DART)-related processes such as germ stem cell renewal and differentiation, meiosis, and embryonic tissue differentiation and growth, support this model's potential to address the need for quicker and more dependable testing methods for DART hazard identification. Organic and inorganic forms of mercury and arsenic had different effects on reproductive-related endpoints in <i>C. elegans</i>, with methylmercury (meHgCl) having effects at lower concentrations than mercury chloride (HgCl₂), and sodium arsenite (NaAsO₂) having effects at lower concentrations than dimethylarsinic acid (DMA). Progeny to adult ratio changes and germline apoptosis were seen at concentrations that also affected gravid adult gross morphology. For both forms of arsenic tested, germline histone regulation was altered at concentrations below those that affected progeny/adult ratios, while concentrations for these two endpoints were similar for the mercury compounds. These <i>C. elegans</i> findings are consistent with corresponding mammalian data, where available, suggesting that small animal model test systems may help to fill critical data gaps by contributing to weight of evidence assessments.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9508968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selecting Normalizers for MicroRNA RT-qPCR Expression Analysis in Murine Preimplantation Embryos and the Associated Conditioned Culture Media.","authors":"David C Hawke,&nbsp;Andrew J Watson,&nbsp;Dean H Betts","doi":"10.3390/jdb11020017","DOIUrl":"https://doi.org/10.3390/jdb11020017","url":null,"abstract":"<p><p>Normalizing RT-qPCR miRNA datasets that encompass numerous preimplantation embryo stages requires the identification of miRNAs that may be used as stable reference genes. A need has also arisen for the normalization of the accompanying conditioned culture media as extracellular miRNAs may serve as biomarkers of embryo developmental competence. Here, we evaluate the stability of six commonly used miRNA normalization candidates, as well as small nuclear U6, using five different means of evaluation (BestKeeper, NormFinder, geNorm, the comparative Delta Ct method and RefFinder comprehensive analysis) to assess their stability throughout murine preimplantation embryo development from the oocyte to the late blastocyst stages, both in whole embryos and the associated conditioned culture media. In descending order of effectiveness, miR-16, miR-191 and miR-106 were identified as the most stable individual reference miRNAs for developing whole CD1 murine preimplantation embryos, while miR-16, miR-106 and miR-103 were ideal for the conditioned culture media. Notably, the widely used U6 reference was among the least appropriate for normalizing both whole embryo and conditioned media miRNA datasets. Incorporating multiple reference miRNAs into the normalization basis via a geometric mean was deemed beneficial, and combinations of each set of stable miRNAs are further recommended, pending validation on a per experiment basis.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9389214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Pronase versus Manual Dechorionation of Zebrafish Embryos for Small Molecule Treatments.","authors":"Eva H Hasegawa,&nbsp;Gist H Farr,&nbsp;Lisa Maves","doi":"10.3390/jdb11020016","DOIUrl":"10.3390/jdb11020016","url":null,"abstract":"<p><p>Zebrafish are a powerful animal model for small molecule screening. Small molecule treatments of zebrafish embryos usually require that the chorion, an acellular envelope enclosing the embryo, is removed in order for chemical compounds to access the embryo from the bath medium. For large-scale studies requiring hundreds of embryos, manual dechorionation, using forceps, can be a time-consuming and limiting process. Pronase is a non-specific protease that is widely used as an enzymatic alternative for dechorionating zebrafish embryos. However, whether pronase treatments alter the effects of subsequent small molecule treatments has not been addressed. Here, we provide a detailed protocol for large-scale pronase dechorionation of zebrafish embryos. We tested whether pronase treatment can influence the efficacy of drug treatments in zebrafish embryos. We used a zebrafish model for Duchenne muscular dystrophy (DMD) to investigate whether the efficacies of trichostatin-A (TSA) or salermide + oxamflatin, small molecule inhibitors known to ameliorate the zebrafish <i>dmd</i> muscle degeneration phenotype, are significantly altered when embryos are treated with pronase versus manual dechorionation. We also tested the effects of pronase on the ability of the anthracycline cancer drug doxorubicin to induce cardiotoxicity in zebrafish embryos. When comparing pronase- versus forceps-dechorionated embryos used in these small molecule treatments, we found no appreciable effects of pronase on animal survival or on the effects of the small molecules. The significant difference that was detected was a small improvement in the ability of salermide + oxamflatin to ameliorate the <i>dmd</i> phenotype in pronase-treated embryos when compared with manual dechorionation. Our study supports the use of pronase treatment as a dechorionation method for zebrafish drug screening experiments.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9382422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Refined Single Cell Landscape of Haematopoiesis in the Mouse Foetal Liver.","authors":"Elena Ceccacci, Emanuela Villa, Fabio Santoro, Saverio Minucci, Christiana Ruhrberg, Alessandro Fantin","doi":"10.3390/jdb11020015","DOIUrl":"10.3390/jdb11020015","url":null,"abstract":"<p><p>During prenatal life, the foetal liver is colonised by several waves of haematopoietic progenitors to act as the main haematopoietic organ. Single cell (sc) RNA-seq has been used to identify foetal liver cell types via their transcriptomic signature and to compare gene expression patterns as haematopoietic development proceeds. To obtain a refined single cell landscape of haematopoiesis in the foetal liver, we have generated a scRNA-seq dataset from a whole mouse E12.5 liver that includes a larger number of cells than prior datasets at this stage and was obtained without cell type preselection to include all liver cell populations. We combined mining of this dataset with that of previously published datasets at other developmental stages to follow transcriptional dynamics as well as the cell cycle state of developing haematopoietic lineages. Our findings corroborate several prior reports on the timing of liver colonisation by haematopoietic progenitors and the emergence of differentiated lineages and provide further molecular characterisation of each cell population. Extending these findings, we demonstrate the existence of a foetal intermediate haemoglobin profile in the mouse, similar to that previously identified in humans, and a previously unidentified population of primitive erythroid cells in the foetal liver.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9382417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principles of Zebrafish Nephron Segment Development.","authors":"Thanh Khoa Nguyen,&nbsp;Madeline Petrikas,&nbsp;Brooke E Chambers,&nbsp;Rebecca A Wingert","doi":"10.3390/jdb11010014","DOIUrl":"https://doi.org/10.3390/jdb11010014","url":null,"abstract":"<p><p>Nephrons are the functional units which comprise the kidney. Each nephron contains a number of physiologically unique populations of specialized epithelial cells that are organized into discrete domains known as segments. The principles of nephron segment development have been the subject of many studies in recent years. Understanding the mechanisms of nephrogenesis has enormous potential to expand our knowledge about the basis of congenital anomalies of the kidney and urinary tract (CAKUT), and to contribute to ongoing regenerative medicine efforts aimed at identifying renal repair mechanisms and generating replacement kidney tissue. The study of the zebrafish embryonic kidney, or pronephros, provides many opportunities to identify the genes and signaling pathways that control nephron segment development. Here, we describe recent advances of nephron segment patterning and differentiation in the zebrafish, with a focus on distal segment formation.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMMD10 Is Essential for Neural Plate Development during Embryogenesis.","authors":"Khanh P Phan, Panayiotis Pelargos, Alla V Tsytsykova, Erdyni N Tsitsikov, Graham Wiley, Chuang Li, Melissa Bebak, Ian F Dunn","doi":"10.3390/jdb11010013","DOIUrl":"10.3390/jdb11010013","url":null,"abstract":"<p><p>The COMMD (copper metabolism MURR1 domain containing) family includes ten structurally conserved proteins (COMMD1 to COMMD10) in eukaryotic multicellular organisms that are involved in a diverse array of cellular and physiological processes, including endosomal trafficking, copper homeostasis, and cholesterol metabolism, among others. To understand the role of COMMD10 in embryonic development, we used <i>Commd10^{Tg(Vav1-icre)A2Kio}</i>/J mice, where the <i>Vav1-cre</i> transgene is integrated into an intron of the <i>Commd10</i> gene, creating a functional knockout of <i>Commd10</i> in homozygous mice. Breeding heterozygous mice produced no COMMD10-deficient <i>(Commd10^Null)</i> offspring, suggesting that COMMD10 is required for embryogenesis. Analysis of <i>Commd10^Null</i> embryos demonstrated that they displayed stalled development by embryonic day 8.5 (E8.5). Transcriptome analysis revealed that numerous neural crest-specific gene markers had lower expression in mutant versus wild-type (WT) embryos. Specifically, <i>Commd10^Null</i> embryos displayed significantly lower expression levels of a number of transcription factors, including a major regulator of the neural crest, <i>Sox10</i>. Moreover, several cytokines/growth factors involved in early embryonic neurogenesis were also lower in mutant embryos. On the other hand, <i>Commd10^Null</i> embryos demonstrated higher expression of genes involved in tissue remodeling and regression processes. Taken together, our findings show that <i>Commd10^Null</i> embryos die by day E8.5 due to COMMD10-dependent neural crest failure, revealing a new and critical role for COMMD10 in neural development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme Oxygenase-1 Is Upregulated during Differentiation of Keratinocytes but Its Expression Is Dispensable for Cornification of Murine Epidermis.","authors":"Marta Surbek, Supawadee Sukseree, Attila Placido Sachslehner, Dragan Copic, Bahar Golabi, Ionela Mariana Nagelreiter, Erwin Tschachler, Leopold Eckhart","doi":"10.3390/jdb11010012","DOIUrl":"10.3390/jdb11010012","url":null,"abstract":"<p><p>The epidermal barrier of mammals is initially formed during embryonic development and continuously regenerated by the differentiation and cornification of keratinocytes in postnatal life. Cornification is associated with the breakdown of organelles and other cell components by mechanisms which are only incompletely understood. Here, we investigated whether heme oxygenase 1 (HO-1), which converts heme into biliverdin, ferrous iron and carbon monoxide, is required for normal cornification of epidermal keratinocytes. We show that HO-1 is transcriptionally upregulated during the terminal differentiation of human keratinocytes in vitro and in vivo. Immunohistochemistry demonstrated expression of HO-1 in the granular layer of the epidermis where keratinocytes undergo cornification. Next, we deleted the <i>Hmox1</i> gene, which encodes HO-1, by crossing <i>Hmox1</i>-floxed and <i>K14-Cre</i> mice. The epidermis and isolated keratinocytes of the resulting <i>Hmox1^f/f K14-Cre</i> mice lacked HO-1 expression. The genetic inactivation of HO-1 did not impair the expression of keratinocyte differentiation markers, loricrin and filaggrin. Likewise, the transglutaminase activity and formation of the stratum corneum were not altered in <i>Hmox1^f/f K14-Cre</i> mice, suggesting that HO-1 is dispensable for epidermal cornification. The genetically modified mice generated in this study may be useful for future investigations of the potential roles of epidermal HO-1 in iron metabolism and responses to oxidative stress.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"11 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}