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The cell lineage of the muscles of the Drosophila head.

Using a cell marker mutation the cell lineage of the muscles of the Drosophila head are traced out. Three sets of muscles separated by lineage restrictions are observed, even when cells are marked as early as the blastoderm stage. Each set underlies the derivatives of one of the three pairs of imaginal discs which differentiate to form the epidermis of the adult head. Clones of the homoeotic mutation engrailed (en10) were apparently normal in the muscles of the head. The muscle clone frequency, at the blastoderm stage, in each hemisegment of the fly is similar, indicating an equal partitioning of cells during segmentation.

Animals↗

Cell lineages of the embryo of the nematode Caenorhabditis elegans.

Embryogenesis of the free-living soil nematode Caenorhabditis elegans produces a juvenile having about 550 cells at hatching. We have determined the lineages of 182 cells by tracing the divisions of individual cells in living embryos. An invariant pattern of cleavage divisions of the egg generates a set of stem cells. These stem cells are the founders of six stem cell lineages. Each lineage has its own clock--i.e., an autonomous rhythm of synchronous cell divisions. The rhythms are maintained in spite of extensive cellular rearrangement. The rate and the orientation of the cell divisions of the cell lineages are essentially invariant among individuals. Thus, the destiny of cells seems to depend primarily on their lineage history. The anterior position of the site of origin of the stem cells in the egg relates to the rate of the cell cycle clock, suggesting intracellular preprogramming of the uncleaved egg. We used a technique that allows normal embryogenesis, from the fertilized egg to hatching, outside the parent under a cover glass. Embryogenesis was followed microscopically with Nomarski interference optics and high-resolution video recording.

Animals↗

Deep haplotype divergence and long-range linkage disequilibrium at xp21.1 provide evidence that humans descend from a structured ancestral population.

Fossil evidence links human ancestry with populations that evolved from modern gracile morphology in Africa 130,000-160,000 years ago. Yet fossils alone do not provide clear answers to the question of whether the ancestors of all modern Homo sapiens comprised a single African population or an amalgamation of distinct archaic populations. DNA sequence data have consistently supported a single-origin model in which anatomically modern Africans expanded and completely replaced all other archaic hominin populations. Aided by a novel experimental design, we present the first genetic evidence that statistically rejects the null hypothesis that our species descends from a single, historically panmictic population. In a global sample of 42 X chromosomes, two African individuals carry a lineage of noncoding 17.5-kb sequence that has survived for >1 million years without any clear traces of ongoing recombination with other lineages at this locus. These patterns of deep haplotype divergence and long-range linkage disequilibrium are best explained by a prolonged period of ancestral population subdivision followed by relatively recent interbreeding. This inference supports human evolution models that incorporate admixture between divergent African branches of the genus Homo.

Biological Evolution↗

Molecular phylogenetics and the evolution of labral spines among eastern Pacific ocenebrine gastropods.

Labral spines are sharp projections of the apertural lip found in some marine gastropods that are used to penetrate hard-shelled prey. The majority of gastropod genera that contain labral spine-bearing species are found in the subfamily Ocenebrinae (Gastropoda: Muricidae). To reconstruct the evolutionary history of labral spine-bearing and labral spine-lacking gastropods in the eastern Pacific (EP) Ocean, partial sequences of two mitochondrial genes (cytochrome oxidase I and 12S rRNA) were obtained from representative taxa. Despite high nucleotide bias, a variety of phylogenetic reconstruction methods produced the same tree topology. The traditional taxonomic view that all "Nucella-like" spine-bearing taxa in the EP belong to a monophyletic "Acanthina" is rejected due to nonmonophyly of this group. The more recently recognized "Acanthinucella" is also not monophyletic, and we therefore propose the new genus Mexacanthina for two Mexican species formerly assigned to Acanthinucella. The genus Ocinebrina, which first appears in the middle Eocene, is not a stem EP ocenebrine lineage and may also not be a monophyletic clade. Tracing the evolutionary history of labral spines among extant lineages indicates that the absence of a labral spine is ancestral for all EP ocenebrines. Ancestral conditions could not be resolved unambiguously for all nodes of the phylogeny based on extant taxa. However, by jointly considering both molecular phylogenetic relationships and the phylogenetic affinities of several extinct taxa, all remaining character state transformation can be inferred unambiguously. Based on this analysis, a labral spine likely evolved independently in at least four lineages of EP ocenebrines. Although homoplasy appears to characterize labral spine evolution among ocenebrine gastropods, the structural position of a labral spine was evolutionarily altered in one lineage, indicating that different types of labral spines do not necessarily reflect convergent evolution.

Animals↗

Cre-mediated recombination in cell lineages that express the progesterone receptor.

Using gene-targeting methods, a progesterone receptor Cre knockin (PR-Cre) mouse was generated in which Cre recombinase was inserted into exon 1 of the PR gene. The insertion positions the Cre gene downstream (and under the specific control) of the endogenous PR promoter. As for heterozygotes for the progesterone receptor knockout (PRKO) mutation, mice heterozygous for the Cre knockin insertion are phenotypically indistinguishable from wildtype. Crossing the PR-Cre with the ROSA26R reporter revealed that Cre excision activity is restricted to cells that express PR in progesterone-responsive tissues such as the uterus, ovary, oviduct, pituitary gland, and mammary gland. Initial characterization of the PR-Cre mouse underscores the utility of this model to precisely ablate floxed target genes specifically in cell lineages that express the PR. In the wider context of female reproductive tissue ontology, this model will be indispensable in tracing the developmental fate of cell lineages that descend from PR positive progenitors.

Animals↗

[Spemann's organizer--it's origin and derivatives (cellular-tissue and molecular-genetic aspects)].

In 1924 H. Spemann and H. Mangold discovered that a piece of the dorsal lip of a blastopore from Triturus cristatus, after transplantation to the ventral side of another embryo, was able to cause the neighbouring tissues to change their fate and participate in the formation of a new embryo. The dorsal lip was termed "the organizer". Since then, for as long as 75 years, attempts have been made to establish the intimate mechanisms of the organizer activity. However, no real advance was achieved in their understanding. Within the last 15 years, genetic and molecular techniques have been vastly improved, to help in tracing the fate of many cell lineages, and in compiling more exactly the fate maps for different parts of the embryo. Using these data, I have attempted to trace the fate of Spemann's organizer after the early gastrula stage. Analysis of data on inductive abilities of the organizer cells, on the use of markers, and on the observation of expression of specific genes allowed to conclude that Spemann's organizer in amphibia and its homologues in other vertebrates too are heterogeneous: they are composed of distinct cell populations able to induce primarity the development of either the head or trunk parts of the embryo. These population, determined to become the head of the trunk organizers still at the blastula stage, may be located either in the single continuous cell layer (as in amphibia and birds) or separated among different tissue germs (as in mammals). When the dorsal-ventral orientation of the embryo is established and the organizer is switched on the very early invaginating cells of the dorsal blastopore lip (in the case of amphibia) move in advance of the entire invaginating mesoderm and by the end of gastrulation occupy the place just in front of the notochord. It is supposed that the early dorsal lip and the prechordal mesoderm (PCM) are one and the same cell population, i.e. during gastrulation Spemann's organizer transfers from the lip of blastopore to the prechordal zone. The PCM seems to play an exclusive role in the formation of a head in vertebrate, because some mutations in genes expressed in the PCM result in the entire head deletion. It is supposed that spreading of differentiating signals from the PCM occurs along the main body axis in both caudal and rostral directions. After the main body plan formation the PCM is replaced by adenohypophysis. This conclusion is drawn not only from the same topology of both these structures, but also from the similarities of a set of specific genetical markers expressed in these, that makes it possible to suppose the existence of deep connections and succession between them. The adenohypophysis seems to arise directly from the PCM, or cells of the ectoderm influenced by the PCM may be subsequently transformed into humoral cells of adenohypophysis. In this interpretation, adenohypophysis and the much earlier established PCM may be considered as derivatives of Spemann's organizer. This inference is supported by the fact that all the three above structures first originate in vertebrates only.

Body Patterning↗

In vitro analysis of position- and lineage-dependent selectivity in the formation of neuromuscular synapses.

The hypotheses that selective formation of nerve-muscle connections depends upon intrinsic cellular properties, endowed either by the cell's rostral-caudal position in the embryo or its lineage, were tested directly in Xenopus embryonic cell cultures. The position or the lineage of embryonic cells was traced in vitro by previous injection of fluorophore-conjugated dextran molecules into individual blastomeres. Synaptic efficacy was assayed by recording synaptic currents from neurite-contacted muscle cells in the culture, and the physical affinity of neurites for muscle cells of different positional or clonal origins was assayed by counting the frequency of association between the neurites' growth cones and the muscle cells. Both assays showed no apparent preference between nerve and muscle cells of similar rostral-caudal positions or clonal origins, suggesting that there is little position- or lineage-dependent selectivity in the initial nerve-muscle interactions.

Animals↗

Evolutionary fingerprints of epithelial-to-mesenchymal transition.

Mesenchymal plasticity has been extensively described in advanced epithelial cancers; however, its functional role in malignant progression is controversial1-5. The function of epithelial-to-mesenchymal transition (EMT) and cell plasticity in tumour heterogeneity and clonal evolution is poorly understood. Here we clarify the contribution of EMT to malignant progression in pancreatic cancer. We used somatic mosaic genome engineering technologies to trace and ablate malignant mesenchymal lineages along the EMT continuum. The experimental evidence clarifies the essential contribution of mesenchymal lineages to pancreatic cancer evolution. Spatial genomic analysis, single-cell transcriptomic and epigenomic profiling of EMT clarifies its contribution to the emergence of genomic instability, including events of chromothripsis. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross-species analysis of pancreatic and other human solid tumours. Mechanistically, we identified that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division. Thus, EMT favours the emergence of genomic-unstable, highly fit tumour cells, which strongly supports the concept of cell-state-restricted patterns of evolution, whereby cancer cell speciation is propagated to progeny within restricted functional compartments. Restraining the evolutionary routes through ablation of clones capable of mesenchymal plasticity, and extinction of the derived lineages, halts the malignant potential of one of the most aggressive forms of human cancer.

Animals↗

Clines of nuclear DNA markers suggest a largely neolithic ancestry of the European gene pool.

Comparisons between archaeological findings and allele frequencies at protein loci suggest that most genes of current Europeans descend from populations that have been expanding in Europe in the last 10, 000 years, in the Neolithic period. Recent mitochondrial data have been interpreted as indicating a much older, Paleolithic ancestry. In a spatial autocorrelation study at seven hypervariable loci in Europe (four microsatellites, two larger, tandem-repeat loci, and a sequence polymorphism) broad clinal patterns of DNA variation were recognized. The observed clines closely match those described at the protein level, in agreement with a possible Near Eastern origin for the ancestral population. Separation times between populations were estimated on the basis of a stepwise mutation model. Even assuming low mutation rates and long generation times, we found no evidence for population splits older than 10,000 years, with the predictable exception of Saami (Lapps). The simplest interpretation of these results is that the current nuclear gene pool largely reflects the westward and northward expansion of a Neolithic group. This conclusion is now supported by purely genetic evidence on the levels and patterns of microsatellite diversity, rather than by correlations of biological and nonbiological data. We argue that many mitochondrial lineages whose origin has been traced back to the Paleolithic period probably reached Europe at a later time.

Cell Nucleus↗

The African diaspora: mitochondrial DNA and the Atlantic slave trade.

Between the 15th and 19th centuries ad, the Atlantic slave trade resulted in the forced movement of approximately 13 million people from Africa, mainly to the Americas. Only approximately 11 million survived the passage, and many more died in the early years of captivity. We have studied 481 mitochondrial DNAs (mtDNAs) of recent African ancestry in the Americas and in Eurasia, in an attempt to trace them back to particular regions of Africa. Our results show that mtDNAs in America and Eurasia can, in many cases, be traced to broad geographical regions within Africa, largely in accordance with historical evidence, and raise the possibility that a greater resolution may be possible in the future. However, they also indicate that, at least for the moment, considerable caution is warranted when assessing claims to be able to trace the ancestry of particular lineages to a particular locality within modern-day Africa.

Black People↗

Characterization of a human plasmacytoma line.

The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough endoplasmatic reticulum (RER). Karyotyping revealed chromosome numbers in the triploid range, with many structural abnormalities, at the 14q32 region among others. A t(14;18) could not be demonstrated. TH was shown to have germline and a rearranged allele for kappa light chain, and only a single rearranged gene for heavy chain immunoglobulin. TH expressed PCA-1, CD9, CD28 and CD38 antigens, HLA class II, RER and kappa light chain, but few or no other antigens associated with the B-cell lineage. Light chain kappa and trace amounts of IgG3 were found intracellularly as well as in culture supernatant. The addition of IL-6 to cultures of TH increased proliferation, as well as the secretion of kappa light chain and the membrane expression of CD28 and CD38 antigens. Because TH has relatively few B cell markers on its membrane, it may be useful for the induction of monoclonal antibodies specific for human plasma cells. It also provides a model for the demonstration that IL-6 can act as a paracrine growth and differentiation factor for cells of myelomal origin.

Adult↗

[The distribution of Y-chromosome haplotypes of Shui ethnic in Sandu,Guizhou].

Non-recombination region of Y-chromosome is a useful marker in tracing evolutionary history of paternal lineage. In the present study, total 92 individuals from Shui ethnic group in Sandu Shui Ethnic Group Autonomous County of Guizhou Province were inspected with 11 SNP sites including M7, M9, M15, M45, M89, M95, M119,M122, M130, M134 and YAP on Y-chromosome.All the subjects were required to be unrelated and without intermarriage with other ethnic groups within three generations. The haplotypes were analyzed by PCR-RFLP method. Four haplotypes H5,H8,H9 and H11 were detected with frequencies of 0.054, 0.044, 0.315 and 0.587, respectively.Principle component indicated that the paternal lineage of Shui ethnic group is much closer to Li ethnic group of Hainan Province and Bouyei ethnic group of Guizhou Province,which belong to the group of Zhuang-Dong branch of Sino-Tibetan language family. In addition genetic study of Shui coincides with its linguistic distribution.

English Abstract↗

Development and distribution of B lineage cells in the domestic cat: analysis with monoclonal antibodies to cat mu-, gamma-, kappa-, and lambda-chains and heterologous anti-alpha antibodies.

To trace the development and distribution of B lineage cells in the domestic cat (Felis catus), we have produced monoclonal antibodies against mu-, gamma-, kappa-, and lambda-chains of feline immunoglobulins (Ig). Goat antibodies against human mu-, alpha-, and lambda-chains, which are reactive with shared determinants on their feline counterparts, were used in conjunction with the panel of mouse monoclonal antibodies. Cytoplasmic mu+ pre-B cells and surface IgM+ B lymphocytes were observed in 42 day fetal liver in which pre-B cells were more abundant than IgM+ B cells. Pre-B cells also were found in bone marrow in young cats, and continued to be generated in the marrow throughout life. In the spleen, adult levels of B cells were attained by 12 wk of age, at which time the frequencies of surface IgM+, IgG+, and lambda+ cells were 49, 3, and 40%, respectively. The distributions of Ig isotypes also were determined among plasma cells as a function of age and tissue localization. IgM plasma cells were predominant in the bone marrow of 1-wk-old cats, whereas IgG plasma cells were the prevalent isotype in adult bone marrow. In the mesenteric lymph nodes of adult animals, the frequency distributions of IgM, IgG, and IgA plasma cells were similar to the frequency distributions of IgM, IgG, and IgA isotypes among bone marrow plasma cells. IgA+ plasma cells predominated in the intestinal lamina propria, in which IgG+ and IgM+ plasma cells were relatively infrequent. In the tissues of both young and adult animals, the ratio of lambda:kappa expression was approximately 3:1. We conclude that the pattern of B cell development in the cat resembles that found in other mammals, except that the kappa to lambda ratio is reversed.

Animals↗

Patterns of cell lineage in the cerebral cortex reveal evidence for developmental boundaries.

Experimental aggregation chimeric mice offer a perspective on cell lineage relationships that is complementary to that of prospective tracing methods such as dye injections or recombinant retroviruses. To create a lineage map of cerebral cortex, the position and genotype of cortical neurons in three-dimensional space were reconstructed with the aid of a computer-assisted mapping system. Chi-square statistical analyses indicate that the spatial distribution of cell lineages in the cerebral cortex is highly nonrandom. When individual dimensions are analyzed separately, a high degree of order is found in the spatial distribution of neuronal genotype ratios in the anterior-posterior dimension but not in the medial-lateral dimension. This suggests an arrangement of lineage-related neurons into "slabs" or "stripes" of cells that are organized in the plane perpendicular to the neuraxis. Additionally, a highly significant variation in genotype ratios was found in the radial dimension (i.e., among cortical cell layers). These data suggest the hypothesis that separate sets of progenitor cells give rise to the superficial and deep layers of cortex. Taken together, our data are consistent with a picture of the developing nervous system in which early developmental restrictions to cell mixing set up boundaries that may be of considerable developmental genetic importance.

Animals↗

huckebein specifies aspects of CNS precursor identity required for motoneuron axon pathfinding.

huckebein encodes a putative zinc finger protein expressed in a subset of Drosophila CNS precursors, including the NB 4-2/GMC 4-2a/RP2 cell lineage. In huckebein mutant embryos, GMC 4-2a does not express the cell fate marker EVEN-SKIPPED; conversely, huckebein overexpression produces a duplicate EVEN-SKIPPED-positive GMC 4-2a. We use Dil to trace the entire NB 4-2 lineage in wild-type and huckebein mutant embryos. Loss of huckebein does not affect the number, position, or type of neurons in the NB 4-2 lineage; however, all motoneurons show axon pathfinding defects and never terminate at the correct muscle. Thus, huckebein regulates aspects of GMC and neuronal identity required for proper motoneuron axon pathfinding in the NB 4-2 lineage.

Animals↗

Glial cell lineages in the rat cerebral cortex.

I have traced the fates of glial cell progenitors in the rat cerebral cortex marked with a recombinant retrovirus throughout most of the period of corticogenesis, from embryonic (E) day 14 to postnatal (P) day 14. Discrete clusters of clonally related glia were examined in serially cut sections, and their phenotypes identified using reliable light and electron microscopic criteria. Analysis of a large number of clones marked with retrovirus at various stages of embryonic life contained, with very few exceptions, either all astrocytes or all oligodendrocytes. This observation suggests that the ventricular zone contains separate progenitor cells for the two glial cell types. Oligodendrocyte clones were rarely seen in the cortices injected with retrovirus at the early stages of corticogenesis (E14-E16), suggesting that there is a very small number of oligodendrocyte progenitors in the ventricular zone at these early stages. Their frequency increased significantly at later embryonic ages. At these later stages, ventricular zone cells also give rise to progenitor cells that make up the subventricular zone in early postnatal life. Injections of retrovirus in this proliferative zone shortly after birth resulted in the generation of labeled astrocyte and oligodendrocyte clones in the cortical gray and white matter, with the astrocyte clones being in the majority. Injections at increasingly later stages resulted in the presence, predominantly in the white matter of both hemispheres and in the corpus callosum, of progressively more oligodendrocyte clones and fewer astrocyte clones. Injections at P14 generated only oligodendrocyte clones in the white matter of both hemispheres. A small number of clusters (<10%) generated after subventricular zone injections contained both astrocytes and oligodendrocytes, suggesting that single subventricular zone cells can differentiate into both glial cell types.

Animals↗

Origins and evolution of methicillin-resistant Staphylococcus aureus clonal lineages.

Most methicillin-resistant Staphylococcus aureus (MRSA) isolates identified among blood isolates collected in Denmark between 1957 and 1970 belonged to either phage group III or the closely related 83A complex and had a PSTM antibiotype (resistance to penicillin [P], streptomycin [S], tetracycline [T], and methicillin [M]). Recently, some of these isolates were shown to have the same genetic backgrounds as contemporary epidemic MRSA isolates, and Danish methicillin-susceptible S. aureus (MSSA) isolates from the 1960s with a PST antibiotype were proposed to have been the recipients of the mecA gene in those lineages. In this study, we investigated the genetic backgrounds of isolates from the 83A complex that were fully susceptible or resistant to penicillin only in order to try to trace the evolutionary trajectory of contemporary MRSA lineages. We also studied MSSA and MRSA isolates from other phage groups in order to investigate if they had the potential to develop into contemporary MRSA clones. Most susceptible or penicillin-resistant isolates from phage group III or the 83A complex belonged to sequence type 8 (ST8) or ST5, while four isolates were ST254. STs 30, 45 and 25 were represented by MSSA isolates from other phage groups, which also included several singletons. Representatives of most of the current major epidemic MRSA lineages were identified among fully susceptible isolates collected in the 1960s, suggesting that these were MSSA lineages which carried genetic traits important for superior epidemicity before the acquisition of methicillin resistance.

Anti-Bacterial Agents↗

Genome evolution in yeasts.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Chromosomes, Fungal↗