- MeSH
- Amylases metabolism MeSH
- Biological Evolution MeSH
- Cyclodextrins metabolism MeSH
- Glycosyltransferases metabolism MeSH
- Publication type
- Review MeSH
Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.
- MeSH
- Cell Lineage MeSH
- Hyperplasia pathology MeSH
- Myocytes, Cardiac pathology physiology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Animals, Newborn * MeSH
- Cell Proliferation MeSH
- Purkinje Fibers * physiopathology physiology pathology MeSH
- Regeneration * physiology MeSH
- Heart Ventricles * pathology physiopathology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolate a pan-LPM enhancer in the zebrafish-specific draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captures the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncover specific activity of zebrafish-derived drl reporters in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.
- MeSH
- Zebrafish MeSH
- Embryo, Nonmammalian MeSH
- Embryonic Induction genetics MeSH
- Gastrulation genetics MeSH
- Intravital Microscopy MeSH
- Mesoderm embryology MeSH
- Zebrafish Proteins genetics MeSH
- Gene Expression Regulation, Developmental * MeSH
- Enhancer Elements, Genetic * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Video-Audio Media MeSH
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAF-mutant lineage becomes a cancerized lineage. The TgCreERT2;BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution.
- MeSH
- Point Mutation MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Mutation genetics MeSH
- Mice MeSH
- Tumor Microenvironment MeSH
- Thyroid Neoplasms * genetics metabolism pathology MeSH
- Thyroid Cancer, Papillary genetics pathology MeSH
- Antineoplastic Agents * MeSH
- Proto-Oncogene Proteins B-raf genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BackgroundThe earliest recognised infections by the SARS-CoV-2 Omicron variant (Pango lineage B.1.1.529) in Belgium and Switzerland suggested a connection to an international water polo tournament, held 12-14 November 2021 in Brno, Czechia.AimTo study the arrival and subsequent spread of the Omicron variant in Belgium and Switzerland, and understand the overall importance of this international sporting event on the number of infections in the two countries.MethodsWe performed intensive forward and backward contact tracing in both countries, supplemented by phylogenetic investigations using virus sequences of the suspected infection chain archived in public databases.ResultsThrough contact tracing, we identified two and one infected athletes of the Belgian and Swiss water polo teams, respectively, and subsequently also three athletes from Germany. In Belgium and Switzerland, four and three secondary infections, and three and one confirmed tertiary infections were identified. Phylogenetic investigation demonstrated that this sporting event played a role as the source of infection, but without a direct link with infections from South Africa and not as a superspreading event; the virus was found to already be circulating at that time in the countries involved.ConclusionThe SARS-CoV-2 Omicron variant started to circulate in Europe several weeks before its identification in South Africa on 24 November 2021. Accordingly, it can be assumed that travel restrictions are usually implemented too late to prevent the spread of newly detected SARS-CoV-2 variants to other regions. Phylogenetic analysis may modify the perception of an apparently clear result of intensive contact tracing.
- MeSH
- COVID-19 * epidemiology MeSH
- Phylogeny MeSH
- Humans MeSH
- SARS-CoV-2 genetics MeSH
- Water Sports * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Belgium MeSH
- Czech Republic MeSH
- Germany MeSH
- Switzerland MeSH
Myxosporea (Myxozoa), a group of parasitic Cnidaria, use mostly bony fishes (Teleostei) as intermediate hosts; however, they can also parasitize other vertebrates such as cartilaginous fish (Chondrichthyes). Molecular data of myxosporeans from sharks and rays (Elasmobranchii) revealed these parasites to be one of the most basal representatives in the myxosporean phylogenetic tree, suggesting their ancient evolutionary history. A new myxosporean species, Bipteria vetusta n. sp., was found in the gall bladder of rabbit fish, Chimaera monstrosa (Holocephali; Chondrichthyes), and ssrDNA-based phylogeny revealed its basal position within the marine myxosporean lineage. Molecular dating based on ssrDNA analysis suggested the origin of a stem lineage leading to the marine myxosporean lineage at the time of the origin of Chondrichthyes in the Silurian era. The two common lineages of Myxozoa, Myxosporea and Malacosporea, were estimated to have split from their common ancestor in the Cambrian era. Tracing the history of evolution of the "vertebrate host type" character in the context of molecular dating showed that cartilaginous fish represented an ancestral state for all myxosporeans. Teleosts were very likely subsequently parasitized by myxozoans four times, independently. Myxosporean radiation and diversification appear to correlate with intermediate host evolution. The first intermediate hosts of myxosporeans were cartilaginous fish. When bony fish evolved and radiated, myxosporeans switched and adapted to bony fish, and subsequently greatly diversified in this new host niche. We believe that the present study is the first attempt at molecular dating of myxozoan evolution based on an old myxosporean species – a living myxosporean fossil.
- MeSH
- Biological Evolution * MeSH
- Phylogeny MeSH
- Host-Parasite Interactions * MeSH
- Molecular Sequence Data MeSH
- Myxozoa classification genetics growth & development isolation & purification MeSH
- DNA, Ribosomal chemistry genetics MeSH
- RNA, Ribosomal, 18S genetics MeSH
- Fishes parasitology MeSH
- Sequence Analysis, DNA MeSH
- Cluster Analysis MeSH
- Gallbladder parasitology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The eleventh annual workshop of the European Network for Breast Development and Cancer, Methods in mammary gland biology and breast cancer, took place on the 16th to 18th of May 2019 in Weggis, Switzerland. The main topics of the meeting were high resolution genomics and proteomics for the study of mammary gland development and cancer, breast cancer signaling, tumor microenvironment, preclinical models of breast cancer, and tissue morphogenesis. Exciting novel findings in, or highly relevant to, mammary gland biology and breast cancer field were presented, with insights into the methods used to obtain them. Among others, the discussed methods included single-cell RNA sequencing, genetic barcoding, lineage tracing, spatial transcriptomics, optogenetics, genetic mouse models and organoids.
- MeSH
- Genomics MeSH
- Carcinogenesis genetics metabolism pathology MeSH
- Humans MeSH
- Tumor Microenvironment * MeSH
- Breast Neoplasms genetics metabolism pathology MeSH
- Proteomics MeSH
- Breast metabolism pathology MeSH
- Signal Transduction MeSH
- Societies, Scientific MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The proper positioning of organs during development is essential, yet little is known about the regulation of this process in mammals. Using murine tooth development as a model, we have found that cell migration plays a central role in positioning of the organ primordium. By combining lineage tracing, genetic cell ablation, and confocal live imaging, we identified a migratory population of Fgf8-expressing epithelial cells in the embryonic mandible. These Fgf8-expressing progenitors furnish the epithelial cells required for tooth development, and the progenitor population migrates toward a Shh-expressing region in the mandible, where the tooth placode will initiate. Inhibition of Fgf and Shh signaling disrupted the oriented migration of cells, leading to a failure of tooth development. These results demonstrate the importance of intraepithelial cell migration in proper positioning of an initiating organ.
- MeSH
- Epithelial Cells cytology metabolism MeSH
- Fibroblast Growth Factors metabolism MeSH
- Mesoderm cytology metabolism MeSH
- Molar cytology embryology metabolism MeSH
- Morphogenesis physiology MeSH
- Mice MeSH
- Odontogenesis physiology MeSH
- Cell Movement physiology MeSH
- Gene Expression Regulation, Developmental physiology MeSH
- Tooth cytology embryology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by using in vivo genetic approaches. Histone H2B-green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytes via both asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid-enhanced micro-computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self-renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilage de novo, entirely substituting fetal chondrocytes.-Li, L., Newton, P. T., Bouderlique, T., Sejnohova, M., Zikmund, T., Kozhemyakina, E., Xie, M., Krivanek, J., Kaiser, J., Qian, H., Dyachuk, V., Lassar, A. B., Warman, M. L., Barenius, B., Adameyko, I., Chagin, A. S. Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.
- MeSH
- Chondrocytes cytology MeSH
- Chondrogenesis * MeSH
- Adult Stem Cells cytology MeSH
- Cartilage, Articular cytology physiology MeSH
- Mice MeSH
- Regeneration MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
