WIREs Mechanisms of Disease最新文献

{"title":"Direct regulation of TCR rearrangement and expression by E proteins during early T cell development.","authors":"Michele K Anderson,&nbsp;Juliana Dutra Barbosa da Rocha","doi":"10.1002/wsbm.1578","DOIUrl":"10.1002/wsbm.1578","url":null,"abstract":"<p><p>γδ T cells are widely distributed throughout mucosal and epithelial cell-rich tissues and are an important early source of IL-17 in response to several pathogens. Like αβ T cells, γδ T cells undergo a stepwise process of development in the thymus that requires recombination of genome-encoded segments to assemble mature T cell receptor (TCR) genes. This process is tightly controlled on multiple levels to enable TCR segment assembly while preventing the genomic instability inherent in the double-stranded DNA breaks that occur during this process. Each TCR locus has unique aspects in its structure and requirements, with different types of regulation before and after the αβ/γδ T cell fate choice. It has been known that Runx and Myb are critical transcriptional regulators of TCRγ and TCRδ expression, but the roles of E proteins in TCRγ and TCRδ regulation have been less well explored. Multiple lines of evidence show that E proteins are involved in TCR expression at many different levels, including the regulation of Rag recombinase gene expression and protein stability, induction of germline V segment expression, chromatin remodeling, and restriction of the fetal and adult γδTCR repertoires. Importantly, E proteins interact directly with the cis-regulatory elements of the TCRγ and TCRδ loci, controlling the predisposition of a cell to become an αβ T cell or a γδ T cell, even before the lineage-dictating TCR signaling events. This article is categorized under: Immune System Diseases > Stem Cells and Development Immune System Diseases > Genetics/Genomics/Epigenetics.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40532913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A compendium of validated pain genes.","authors":"Eric Wistrom,&nbsp;Rebecca Chase,&nbsp;Patrick R Smith,&nbsp;Zachary T Campbell","doi":"10.1002/wsbm.1570","DOIUrl":"https://doi.org/10.1002/wsbm.1570","url":null,"abstract":"<p><p>The development of novel pain therapeutics hinges on the identification and rigorous validation of potential targets. Model organisms provide a means to test the involvement of specific genes and regulatory elements in pain. Here we provide a list of genes linked to pain-associated behaviors. We capitalize on results spanning over three decades to identify a set of 242 genes. They support a remarkable diversity of functions spanning action potential propagation, immune response, GPCR signaling, enzymatic catalysis, nucleic acid regulation, and intercellular signaling. Making use of existing tissue and single-cell high-throughput RNA sequencing datasets, we examine their patterns of expression. For each gene class, we discuss archetypal members, with an emphasis on opportunities for additional experimentation. Finally, we discuss how powerful and increasingly ubiquitous forward genetic screening approaches could be used to improve our ability to identify pain genes. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.","authors":"David M Engelhardt,&nbsp;Cara A Martyr,&nbsp;Lee Niswander","doi":"10.1002/wsbm.1559","DOIUrl":"https://doi.org/10.1002/wsbm.1559","url":null,"abstract":"<p><p>Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three-dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide. Though NTDs are all defined as incomplete closure of the neural tube, the pathogenesis of an NTD determines the type, severity, positioning, and accompanying phenotypes. In this review, we survey pathogenesis of NTDs relating to disruption of cellular processes arising from genetic mutations, altered epigenetic regulation, and environmental influences by micronutrients and maternal condition. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605354/pdf/nihms-1799087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and diseases of the coronary microvasculature and its communication with the myocardium.","authors":"Kristýna Neffeová,&nbsp;Veronika Olejníčková,&nbsp;Ondřej Naňka,&nbsp;Hana Kolesová","doi":"10.1002/wsbm.1560","DOIUrl":"https://doi.org/10.1002/wsbm.1560","url":null,"abstract":"<p><p>We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development. We summarize knowledge about establishing the heart microvasculature density based on diffusion distance. Then signaling mechanisms which are involved in forming the microvasculature are discussed. This includes details of cardiomyocyte-endothelial cell interactions involving hypoxia, VEGF, NOTCH, angiopoietin, PDGF, and other signaling factors. The microvasculature is understudied due to difficulties in its visualization. Therefore, currently available imaging methods to delineate the coronary microvasculature in development and in adults are discussed. The second part of the review is dedicated to the importance of the coronary vasculature in disease. Coronary microvasculature pathologies are present in many congenital heart diseases (CHD), especially in pulmonary atresia, and worsen outcomes. In CHDs, where the development of the myocardium is impaired, microvasculature is also affected. In adult patients coronary microvascular disease is one of the main causes of sudden cardiac death, especially in women. Coronary microvasculature pathologies affect myocardial ischemia and vice versa; myocardial pathologies such as cardiomyopathies are closely connected with coronary microvasculature dysfunction. Microvasculature inflammation also worsens the outcomes of COVID-19 disease. Our review stresses the importance of coronary microvasculature and provides an overview of its formation and signaling mechanisms and the importance of coronary vasculature pathologies in CHDs and adult diseases. This article is categorized under: Cardiovascular Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40164570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems biology of angiogenesis signaling: Computational models and omics.","authors":"Yu Zhang,&nbsp;Hanwen Wang,&nbsp;Rebeca Hannah M Oliveira,&nbsp;Chen Zhao,&nbsp;Aleksander S Popel","doi":"10.1002/wsbm.1550","DOIUrl":"https://doi.org/10.1002/wsbm.1550","url":null,"abstract":"<p><p>Angiogenesis is a highly regulated multiscale process that involves a plethora of cells, their cellular signal transduction, activation, proliferation, differentiation, as well as their intercellular communication. The coordinated execution and integration of such complex signaling programs is critical for physiological angiogenesis to take place in normal growth, development, exercise, and wound healing, while its dysregulation is critically linked to many major human diseases such as cancer, cardiovascular diseases, and ocular disorders; it is also crucial in regenerative medicine. Although huge efforts have been devoted to drug development for these diseases by investigation of angiogenesis-targeted therapies, only a few therapeutics and targets have proved effective in humans due to the innate multiscale complexity and nonlinearity in the process of angiogenic signaling. As a promising approach that can help better address this challenge, systems biology modeling allows the integration of knowledge across studies and scales and provides a powerful means to mechanistically elucidate and connect the individual molecular and cellular signaling components that function in concert to regulate angiogenesis. In this review, we summarize and discuss how systems biology modeling studies, at the pathway-, cell-, tissue-, and whole body-levels, have advanced our understanding of signaling in angiogenesis and thereby delivered new translational insights for human diseases. This article is categorized under: Cardiovascular Diseases > Computational Models Cancer > Computational Models.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39636617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New developments in the biology of fibroblast growth factors.","authors":"David M Ornitz,&nbsp;Nobuyuki Itoh","doi":"10.1002/wsbm.1549","DOIUrl":"https://doi.org/10.1002/wsbm.1549","url":null,"abstract":"<p><p>The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltage-gated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology Congenital Diseases > Stem Cells and Development Cancer > Stem Cells and Development.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115509/pdf/nihms-1890656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterning of the antero-ventral mammalian brain: Lessons from holoprosencephaly comparative biology in man and mouse.","authors":"Kristen S Barratt,&nbsp;Kyle A Drover,&nbsp;Zoe M Thomas,&nbsp;Ruth M Arkell","doi":"10.1002/wsbm.1552","DOIUrl":"https://doi.org/10.1002/wsbm.1552","url":null,"abstract":"<p><p>Adult form and function are dependent upon the activity of specialized signaling centers that act early in development at the embryonic midline. These centers instruct the surrounding cells to adopt a positional fate and to form the patterned structures of the phylotypic embryo. Abnormalities in these processes have devastating consequences for the individual, as exemplified by holoprosencephaly in which anterior midline development fails, leading to structural defects of the brain and/or face. In the 25 years since the first association between human holoprosencephaly and the sonic hedgehog gene, a combination of human and animal genetic studies have enhanced our understanding of the genetic and embryonic causation of this congenital defect. Comparative biology has extended the holoprosencephaly network via the inclusion of gene mutations from multiple signaling pathways known to be required for anterior midline formation. It has also clarified aspects of holoprosencephaly causation, showing that it arises when a deleterious variant is present within a permissive genome, and that environmental factors, as well as embryonic stochasticity, influence the phenotypic outcome of the variant. More than two decades of research can now be distilled into a framework of embryonic and genetic causation. This framework means we are poised to move beyond our current understanding of variants in signaling pathway molecules. The challenges now at the forefront of holoprosencephaly research include deciphering how the mutation of genes involved in basic cell processes can also cause holoprosencephaly, determining the important constituents of the holoprosencephaly permissive genome, and identifying environmental compounds that promote holoprosencephaly. This article is categorized under: Congenital Diseases > Stem Cells and Development Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Molecular and Cellular Physiology Congenital Diseases > Environmental Factors.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39778499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of gut microbiota in infectious diseases.","authors":"Yongjie Cai,&nbsp;Lingming Chen,&nbsp;Sien Zhang,&nbsp;Lingchan Zeng,&nbsp;Gucheng Zeng","doi":"10.1002/wsbm.1551","DOIUrl":"https://doi.org/10.1002/wsbm.1551","url":null,"abstract":"<p><p>The intestine, the largest immune organ in the human body, harbors approximately 10¹³ microorganisms, including bacteria, fungi, viruses, and other unknown microbes. The intestine is a most important crosstalk anatomic structure between the first (the host) and second (the microorganisms) genomes. The imbalance of the intestinal microecology, especially dysbiosis of the composition, structure, and function of gut microbiota, is linked to human diseases. In this review, we investigated the roles and underlying mechanisms of gut microecology in the development, progression, and prognosis of infectious diseases. Furthermore, we discussed potential new strategies of prevention and treatment for infectious diseases based on manipulating the composition, structure, and function of intestinal microorganisms in the future. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39777667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke.","authors":"Alexandra M Kaloss,&nbsp;Michelle H Theus","doi":"10.1002/wsbm.1553","DOIUrl":"https://doi.org/10.1002/wsbm.1553","url":null,"abstract":"<p><p>Arterial collateralization, as determined by leptomeningeal anastomoses or pial collateral vessels, is a well-established vital player in cerebral blood flow restoration and neurological recovery from ischemic stroke. A secondary network of cerebral collateral circulation apart from the Circle of Willis, exist as remnants of arteriole development that connect the distal arteries in the pia mater. Recent interest lies in understanding the cellular and molecular adaptations that control the growth and remodeling, or arteriogenesis, of these pre-existing collateral vessels. New findings from both animal models and human studies of ischemic stroke suggest a multi-factorial and complex, temporospatial interplay of endothelium, immune and vessel-associated cell interactions may work in concert to facilitate or thwart arteriogenesis. These valuable reports may provide critical insight into potential predictors of the pial collateral response in patients with large vessel occlusion and may aid in therapeutics to enhance collateral function and improve recovery from stroke. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/9f/WSBM-14-e1553.PMC9283306.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39888541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition to extrauterine life and the modeling of perinatal asphyxia in rats.","authors":"M. Ortiz, F. Loidl, Pablo Vázquez-Borsetti","doi":"10.1002/wsbm.1568","DOIUrl":"https://doi.org/10.1002/wsbm.1568","url":null,"abstract":"Generation of murine models for the study of birth-related pathologies has proven to be a complex and controversial problem. Differences in the relative timing of developmental events of both species have led some researchers to suggest that the rat is born comparatively less developed than the human. The solution proposed to this problem would consist in the delay of the experiments of perinatal asphyxia (PA), usually up to 7-10 days, allowing developmental levels to \"equalize\" with the human at birth. This solution generates a new set of problems. The developmental milestones in both species follow a divergent temporal pattern. Increasing the age of the rat not only can improve resemblance with humans but also will make the model miss a crucial set of milestones related to birth. During this process, there are specific mechanisms to protect the fetus from neuronal damage, especially those caused by asphyxia. These factors are not present in models where the asphyxia is delayed. In these models, there will be more false positives and more damage that would not be present in humans exposed to PA. This article is categorized under: Cancer > Stem Cells and Development Congenital Diseases > Environmental Factors Neurological Diseases > Environmental Factors.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49363888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}