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At least 37 records · Page 2Linked to original sources
PubMed2003

Transcriptional regulation of glial cell specification.

Neuronal differentiation relies on proneural factors that also integrate positional information and contribute to the specification of the neuronal type. The molecular pathway triggering glial specification is not understood yet. In Drosophila, all lateral glial precursors and glial-promoting activity have been identified, which provides us with a unique opportunity to dissect the regulatory pathways controlling glial differentiation and specification. Although glial lineages are very heterogeneous with respect to position, time of differentiation, and lineage tree, they all express and require two homologous genes, glial cell deficient/glial cell missing (glide/gcm) and glide2, that act in concert, with glide/gcm constituting the major glial-promoting factor. Here, we show that glial specification resides in glide/gcm transcriptional regulation. The glide/gcm promoter contains lineage-specific elements as well as quantitative and turmoil elements scattered throughout several kilobases. Interestingly, there is no correlation between a specific regulatory element and the type of glial lineage. Thus, the glial-promoting factor acts as a naive switch-on button that triggers gliogenesis in response to multiple pathways converging onto its promoter. Both negative and positive regulation are required to control glide/gcm expression, indicating that gliogenesis is actively repressed in some neural lineages.

Animals↗
PubMed2006

Time-lapse tracing of mitotic cell divisions in the early Xenopus embryo using microscopic MRI.

Mitotic cell division is a highly regulated cellular event in all organisms, but its direct visualization in the vertebrates is limited to animals with transparent embryos. Here, we report on the use of microscopic magnetic resonance imaging (mMRI) to noninvasively observe mitotic cell division of early blastomeres in the optically opaque Xenopus laevis embryo. Due to intrinsic tissue contrast, cell nuclei can be directly visualized without the need for contrast enhancing labeling. By taking two-dimensional in vivo time-lapse image sequences, the karyokinesis of a blastomere is followed. Timing and orientation of the cleavages can be traced for five cell divisions to establish a cell lineage tree, including orientation and timing of the mitosis. This work demonstrates for the first time the use of MRI for the visualization of cell divisions and expands the experimental scope of the Xenopus embryo.

Animals↗
PubMed2002

What cell lineages tell us about the evolution of spiralia remains to be seen.

Cell-lineage trees may contain information about spiralian phylogeny, as proposed by Guralnick and Lindberg (2001). Here we discuss this possibility further and conclude that the cell-division pattern must be known in greater detail and the coding methods refined before a possible phylogenetic signal can be identified.

Animals↗
PubMed2005

Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells.

It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand.

Actins↗
PubMed2006

Automated cell lineage construction: a rapid method to analyze clonal development established with murine neural progenitor cells.

Understanding cell lineage relationships is fundamental to understanding development, and can shed light on disease etiology and progression. We present a method for automated tracking of lineages of proliferative, migrating cells from a sequence of images. The method is applicable to image sequences gathered either in vitro or in vivo. Currently, generating lineage trees from progenitor cells over time is a tedious, manual process, which limits the number of cell measurements that can be practically analyzed. In contrast, the automated method is rapid and easily applied, and produces a wealth of measurements including the precise position, shape, cell-cell contacts, motility and ancestry of each cell in every frame, and accurate timings of critical events, e.g., mitosis and cell death. Furthermore, it automatically produces graphical output that is immediately accessible. Application to clonal development of mouse neural progenitor cells growing in cell culture reveals complex changes in cell cycle rates during neuron and glial production. The method enables a level of quantitative analysis of cell behavior over time that was previously infeasible.

Algorithms↗
PubMed1980

The random character of protein evolution and its effects on the reliability of phylogenetic information deduced from amino acid sequences and compositions.

Because evolution occurs by random events, the actual number of substitutions that occur in any period is not exactly equal to the number expected from the mean rate of substitution, but is statistically distributed about it. In consequence, even if rates of evolution are constant in different lineages, 'trees' deduced from descendant protein sequences contain random errors. When there are fewer than about eight differences between the sequences of the most distantly related pair from a set of proteins, this random effect is very large. It can then render trivial the statistical disadvantage inherent in using a crude measure of protein difference, such as amino acid composition or immunological cross-reactivity, in preference to a measure based the sequences of the most distantly related pair from a set of proteins, this random effect is very large. It can then render trivial the statistical disadvantage inherent in using a crude measure of protein difference, such as amino acid composition or immunological cross-reactivity, in preference to a measure based the sequences of the most distantly related pair from a set of proteins, this random effect is very large. It can then render trivial the statistical disadvantage inherent in using a crude measure of protein difference, such as amino acid composition or immunological cross-reactivity, in preference to a measure based on amino acid sequence. In some cases, such as classification of mammals on the basis of cytochrome c structure, it appears to make little difference to the reliability of the results whether the sequences of the protein concerned are known or not. It may also be possible to obtain more reliable phylogenetic information from composition measurements on several kinds of protein than one could obtain from sequence measurements on a single kind of protein.

Amino Acid Sequence↗
PubMed1997

Evolution and phylogeny of the Diptera: a molecular phylogenetic analysis using 28S rDNA sequences.

Portions of the large ribosomal subunit RNA gene (28S rDNA) encompassing the D1 and the D7 region were obtained from 16 dipteran species and families to reconstruct early phylogenetic events in the order Diptera. For outgroup comparison, the corresponding sequences were used from representative taxa of the Siphonaptera, Mecoptera, and Lepidoptera. A subset of 488 unambiguously alignable sites was analyzed with respect to important sequence evolution parameters. We found (1) sequence variability is significantly higher in double-stranded sites than in single-stranded sites, (2) transitions are close to saturation in most pairwise sequence comparisons, (3) significant substitution rate heterogeneity exists across sites, and (4) significant substitution rate heterogeneity exists among lineages. Tree reconstruction was carried out with the neighbor joining, maximum parsimony, and maximum likelihood methods. Four major subgroups are consistently and robustly supported: the Brachycera, the Culicomorpha, the Tipulomorpha sensu stricto, and the hitherto controversial Bibionomorpha sensu lato, which includes the families Sciaridae, Mycetophilidae, Cecidomyiidae, Bibionidae, Scatopsidae, and Anisopodidae. The phylogenetic relationships within or among these subclades and the positions of the families Psychodidae and Trichoceridae were not robustly resolved. These results support the view that the mouthparts of extant dipteran larvae evolved from a derived ground state characterized by subdivided and obliquely moving mandibles. Furthermore, sequence divergence and the paleontological record consistently indicate that a period of rapid cladogenesis gave rise to the major dipteran subgroups.

Animals↗
PubMed1981

Strategies for control of pattern formation in Caenorhabditis elegans.

In this paper, strategies for controlling pattern formation in Caenorhabditis elegans are reviewed. The somatic tissues of this small nematode develop, in large part, by invariant cell lineages, whereas the germ-line tissue arises primarily by a variable pattern of divisions. The spatial organization of the germ-line tissue depends on special regulatory cells, the distal tip cells, which appear to influence nearby germ cells to remain in mitosis. In somatic tissues, the problem of specifying that a cell in a particular position assumes a particular fate seems to be controlled by a number of different strategies. These include the production of non-equivalent cells in particular positions of the lineage tree, local interactions between apparently equivalent cells in close contact, and the influence of another special regulatory cell, the anchor cell, over certain neighbouring cells.

Animals↗
PubMedDate not supplied

Clinical practice and future needs in recombinant human granulocyte colony-stimulating factor treatment: a review of randomized trials in clinical haemato-oncology.

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) may have a significant impact on preventing infections associated with chemotherapy-induced neutropenia, as well as shortening time to tree lineage engraftment following high-dose chemotherapy and progenitor transplantation. However, the scientific literature documenting evidence-based practice is insufficient and often misinterpreted. This review presents data and discusses the evidence for actual clinical practice in the use of rHuG-CSF in conventional cyclic chemotherapy, either prophylactic or therapeutic, and high-dose therapy, either in priming for mobilization or post-transplantation. In the past decade, many reports have based their conclusions on surrogate markers, and it is time to move towards evaluation of clinically relevant factors. Data must be generated prospectively based on current clinical practice, and several issues must be considered and evaluated to define the true clinical benefit of rHuG-CSF with or without stem-cell support. Evaluation should include complications and needs for resources as well as impact on toxicity and efficacy of conventional or high-dose chemotherapy.

Antineoplastic Agents↗
PubMed2003

Monitoring neural progenitor fate through multiple rounds of division in an intact vertebrate brain.

The behaviour of neural progenitors in the intact vertebrate brain and spinal cord is poorly understood, chiefly because of the inaccessibility and poor optical qualities inherent in many model systems. To overcome these problems we have studied the optically superior brain of the zebrafish embryo and have monitored the in vivo behaviour of fluorescently labelled neural progenitors and their daughter cells throughout a substantial period of hindbrain development. We find the majority (84%) of hindbrain neurons are born from progenitor divisions that generate two neurons and 68% of reconstructed lineage trees contained no asymmetric stem cell-like divisions. No progenitors divided in the manner expected of a classic stem cell; i.e. one that repeatedly self-renews and generates a differentiated cell type by asymmetric division. We also analysed the orientation of progenitor divisions relative to the plane of the ventricular zone (VZ) and find that this does not correlate with the fate of the daughter cells. Our results suggest that in this vertebrate system the molecular determinants that control whether a cell will become a neuron are usually not linked to a mechanism that generates asymmetric divisions.

Animals↗
PubMed2002

Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts.

Stem cells and neuroblasts derived from mouse embryos undergo repeated asymmetric cell divisions, generating neural lineage trees similar to those of invertebrates. In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates. We investigated whether a mouse homologue m-numb had a similar role during mouse cortical development. Progenitor cells isolated from the embryonic mouse cortex were followed as they underwent their next cell division in vitro. Numb distribution was predominantly asymmetric during asymmetric cell divisions yielding a beta-tubulin III(-) progenitor and a beta-tubulin III(+) neuronal cell (P/N divisions) and predominantly symmetric during divisions producing two neurons (N/N divisions). Cells from the numb knockout mouse underwent significantly fewer asymmetric P/N divisions compared to wild type, indicating a causal role for Numb. When progenitor cells derived from early (E10) cortex undergo P/N divisions, both daughters express the progenitor marker Nestin, indicating their immature state, and Numb segregates into the P or N daughter with similar frequency. In contrast, when progenitor cells derived from later E13 cortex (during active neurogenesis in vivo) undergo P/N divisions they produce a Nestin(+) progenitor and a Nestin(-) neuronal daughter, and Numb segregates preferentially into the neuronal daughter. Thus during mouse cortical neurogenesis, as in Drosophila neurogenesis, asymmetric segregation of Numb could inhibit Notch activity in one daughter to induce neuronal differentiation. At terminal divisions generating two neurons, Numb was symmetrically distributed in approximately 80% of pairs and asymmetrically in 20%. We found a significant association between Numb distribution and morphology: most sisters of neuron pairs with symmetric Numb were similar and most with asymmetric Numb were different. Developing cortical neurons with Numb had longer processes than those without. Numb is expressed by neuroblasts and stem cells and can be asymmetrically segregated by both. These data indicate Numb has an important role in generating asymmetric cell divisions and diverse cell fates during mouse cortical development.

Animals↗
PubMed1987

Cell lineage, cell death, and the developmental origin of identified serotonin- and dopamine-containing neurons in the leech.

The nervous system of the glossiphoniid leech includes segmentally iterated neurons that contain serotonin (5-HT) and dopamine. These have been investigated in Helobdella triserialis, Theromyzon rude, and Haementeria ghilianii. Five types of 5-HT neurons are identified by immunocytochemistry in the abdominal ganglia of the ventral nerve cord: the bilaterally paired Retzius, anteromedial, ventrolateral and dorsolateral neurons, and the unpaired posteromedial (pm) neuron. Three types of bilaterally paired dopamine neurons are identified by glyoxylic acid-induced fluorescence in the segmental body wall: MD, LD1, and LD2. Each left or right half of the segmental complement of the leech nervous system is known to develop from 6 distinct ectodermal primary blast cells (ns, nf, o, p, qs, and qf). To identify the blast cells of origin of the 5-HT and dopamine neurons, fluorescent cell lineage tracers were injected into the various precursors of the blast cells in early (stage 6) embryos. The embryos were then raised until their 5-HT and dopamine neurons could be scored (stage 11) for the presence or absence of lineage tracer. We find that the Retzius, anteromedial, and posteromedial 5-HT neurons are derived from the ns blast cell, while the ventrolateral and dorsolateral 5-HT neurons are derived from the nf blast cell. The unpaired pm 5-HT neuron arises as one of a bilateral pair of neurons, of which one later dies. Whether the left or right pm neuron survives in any given ganglion is the consequence of some form of competitive interaction between cells derived from the left and right n primary blast cells, possibly between the left and right pm neurons themselves. We find that, of the dopamine neurons, the LD1 neuron is derived from the o blast cell, the LD2 neurons from the p blast cell, and the MD neuron from one of the 2 kinds of q blast cells. These results show that the 5-HT and dopamine neurons arise from 5 different primary blast cells in a highly determinate manner, and they support the view that cells of a similar phenotype need not be closely related in the developmental cell lineage tree.

Animals↗
PubMed2006

Polyploids with different origins and ancestors form a single sexual polyploid species.

Polyploidization is one of the few mechanisms that can produce instantaneous speciation. Multiple origins of tetraploid lineages from the same two diploid progenitors are common, but here we report the first known instance of a single tetraploid species that originated repeatedly from at least three diploid ancestors. Parallel evolution of advertisement calls in tetraploid lineages of gray tree frogs has allowed these lineages to interbreed, resulting in a single sexually interacting polyploid species despite the separate origins of polyploids from different diploids. Speciation by polyploidization in these frogs has been the source of considerable debate, but the various published hypotheses have assumed that polyploids arose through either autopolyploidy or allopolyploidy of extant diploid species. We utilized molecular markers and advertisement calls to infer the origins of tetraploid gray tree frogs. Previous hypotheses did not sufficiently account for the observed data. Instead, we found that tetraploids originated multiple times from extant diploid gray tree frogs and two other, apparently extinct, lineages of tree frogs. Tetraploid lineages then merged through interbreeding to result in a single species. Thus, polyploid species may have complex origins, especially in systems in which isolating mechanisms (such as advertisement calls) are affected directly through hybridization and polyploidy.

Animals↗
PubMed2001

Mitochondrial DNA polymorphisms in Yunnan nationalities in China.

Nucleotide sequences of the D-loop region of human mitochondrial DNA from four Yunnan nationalities, Dai, Wa, Lahu, and Tibetan, were analyzed. Based on a comparison of 563-bp sequences in 99 people, 66 different sequence types were observed. Of these, 64 were unique to their respective populations, whereas only 2 types were shared between the Lahu and Wa nationalities. The D-loop sequence variation and phylogenetic analysis suggested that the 99 mtDNA lineages were classified into eight clusters in the phylogenetic tree. All lineages that had a 9-bp deletion in the COII/tRNALYs intergenic region appeared in one cluster in the D-loop tree, suggesting a single event of the deletion in the Yunnan nationalities studied. Genetic distances, based on net nucleotide diversities between populations including Han Chinese and mainland Japanese, revealed that the Dai, Wa, Lahu, and Han Chinese are closely related to each other, while Tibetan and mainland Japanese formed a single cluster. The bootstrap probability of separation between the Dai-Wa-Lahu-Chinese clade and the Tibetan-Japanese clade was 99%, indicating that there are at least two different origins among minority groups in Yunnan province. Although the genetic distance between Tibetan and Japanese within the clade is rather long, the results may shed light on the origins of mainland Japanese.

Base Sequence↗
PubMed2004

Where west meets east: the complex mtDNA landscape of the southwest and Central Asian corridor.

The southwestern and Central Asian corridor has played a pivotal role in the history of humankind, witnessing numerous waves of migration of different peoples at different times. To evaluate the effects of these population movements on the current genetic landscape of the Iranian plateau, the Indus Valley, and Central Asia, we have analyzed 910 mitochondrial DNAs (mtDNAs) from 23 populations of the region. This study has allowed a refinement of the phylogenetic relationships of some lineages and the identification of new haplogroups in the southwestern and Central Asian mtDNA tree. Both lineage geographical distribution and spatial analysis of molecular variance showed that populations located west of the Indus Valley mainly harbor mtDNAs of western Eurasian origin, whereas those inhabiting the Indo-Gangetic region and Central Asia present substantial proportions of lineages that can be allocated to three different genetic components of western Eurasian, eastern Eurasian, and south Asian origin. In addition to the overall composite picture of lineage clusters of different origin, we observed a number of deep-rooting lineages, whose relative clustering and coalescent ages suggest an autochthonous origin in the southwestern Asian corridor during the Pleistocene. The comparison with Y-chromosome data revealed a highly complex genetic and demographic history of the region, which includes sexually asymmetrical mating patterns, founder effects, and female-specific traces of the East African slave trade.

Asia, Central↗
PubMed1991

Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events.

An algorithm, 'phylogenetic scanning', is described for mapping gene conversion events where comparative DNA sequence data are available from different species. In this algorithm, sets of hypothetical phylogenetic trees are constructed that describe possible sequence relationships due to gene conversions in different species lineages; these trees are then evaluated by the principle of parsimony at intervals in the sequence alignment. When used to map gene conversion events that occurred between the pair of gamma-globin genes of higher primates, the algorithm gives results nearly identical to those obtained using a tedious manual approach. Suggestions are also provided for adaptation of this procedure to the analysis of other recombination events.

Algorithms↗
PubMed2024

A framework for automated scalable designation of viral pathogen lineages from genomic data.

Pathogen lineage nomenclature systems are a key component of effective communication and collaboration for researchers and public health workers. Since February 2021, the Pango dynamic lineage nomenclature for SARS-CoV-2 has been sustained by crowdsourced lineage proposals as new isolates were sequenced. This approach is vulnerable to time-critical delays as well as regional and personal bias. Here we developed a simple heuristic approach for dividing phylogenetic trees into lineages, including the prioritization of key mutations or genes. Our implementation is efficient on extremely large phylogenetic trees consisting of millions of sequences and produces similar results to existing manually curated lineage designations when applied to SARS-CoV-2 and other viruses including chikungunya virus, Venezuelan equine encephalitis virus complex and Zika virus. This method offers a simple, automated and consistent approach to pathogen nomenclature that can assist researchers in developing and maintaining phylogeny-based classifications in the face of ever-increasing genomic datasets.

Animals↗
PubMed2004

Nuclear DNA phylogeny of the squirrels (Mammalia: Rodentia) and the evolution of arboreality from c-myc and RAG1.

Although the family Sciuridae is large and well known, phylogenetic analyses are scarce. We report on a comprehensive molecular phylogeny for the family. Two nuclear genes (c-myc and RAG1) comprising approximately 4500 bp of data (most in exons) are applied for the first time to rodent phylogenetics. Parsimony, likelihood, and Bayesian analyses of the separate gene regions and combined data reveal five major lineages and refute the conventional elevation of the flying squirrels (Pteromyinae) to subfamily status. Instead, flying squirrels are derived from one of the tree squirrel lineages. C-myc indels corroborate the sequence-based topologies. The common ancestor of extant squirrels appears to have been arboreal, confirming the fossil evidence. The results also reveal an unexpected clade of mostly terrestrial squirrels with African and Holarctic centers of diversity. We present a revised classification of squirrels. Our results demonstrate the phylogenetic utility of relatively slowly evolving nuclear exonic data even for relatively recent clades.

Animals↗