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At least 955 records · Page 53Linked to original sources
PubMed2006

Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium.

The murine olfactory epithelium (OE) generates olfactory receptor neurons (ORNs) throughout development and into adulthood, but only a few of the factors regulating olfactory neuro- and glio-genesis have been delineated. Notch receptors maintain CNS neuronal progenitors and drive glial differentiation, and the Notch effectors Hes 1 and 5 are expressed in the OE, but the Notch receptors that stimulate Hes gene activation in defined lineages during OE development have not been determined. Here, we first use RT-PCR to reveal which Notch receptors and ligands are expressed in the developing and adult OE. This is followed by immunofluorescent detection, combined with lineage-specific markers to define the stage-specific developmental expression of different Notch family members. We show that throughout development, Notch 1 and 3 are expressed in cells retained within the lamina propria, where Notch 3 is expressed in olfactory ensheathing cells (OECs). In contrast, Notch 2 is expressed in apical embryonic and early postnatal OE neuronal progenitors. In postnatal and adult OE, Notch 1 is expressed predominantly in Bowman's glands, and Notch 2 in sustentacular cells. Notch 2 and Notch 1/3 may, therefore, have different roles in the commitment and differentiation of neuronal and glial lineages of the OE during development, and the maintenance of non-neuronal phenotypes postnatally.

Animals↗
PubMed2007

BMP and LIF signaling coordinately regulate lineage restriction of radial glia in the developing forebrain.

The earliest radial glia are neural stem cells that guide neural cell migration away from ventricular zones. Subsequently, radial glia become lineage restricted during development before they differentiate into more mature cell types in the CNS. We have previously shown that subpopulations of radial glial cells express markers for glial and neuronal restricted precursors (GRPs and NRPs) in expression patterns that are temporally and spatially regulated during CNS development. To characterize further the mechanism of this regulation in rat forebrain, we tested whether secreted factors that are present during development effect lineage restriction of radial glia. We show here that in radial glial cultures LIF/CNTF up-regulates, whereas BMP2 down-regulates GRP antigens recognized by monoclonal antibodies A2B5/4D4. These activities combined with secretion of BMPs dorsally and LIF/CNTF from the choroid plexus provide an explanation for the graded distribution pattern of A2B5/4D4 in dorso-lateral ventricular regions in vivo. The regulation by LIF/CNTF of A2B5/4D4 is mediated through the JAK-STAT pathway. BMP2 promotes expression on radial glial cells of the NRP marker polysialic acid most likely by regulating N-CAM expression itself, as well as at least one polysialyl transferase responsible for synthesis of polysialic acid on N-CAM. Taken together, these results suggest that generation of lineage-restricted precursors is coordinately regulated by gradients of the secreted factors BMPs and LIF/CNTF during development of dorsal forebrain.

Animals↗
PubMed2007

Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination.

Insulin-like growth factor-I (IGF-I) has been shown to be a potent agent in promoting the growth and differentiation of oligodendrocyte precursors, and in stimulating myelination during development and following injury. To definitively determine whether IGF-I acts directly on the cells of oligodendrocyte lineage, we generated lines of mice in which the type 1 IGF receptor gene (igf1r) was conditionally ablated either in Olig1 or proteolipid protein expressing cells (termed IGF1R(pre-oligo-ko) and IGF1R(oligo-ko) mice, respectively). Compared with wild type mice, IGF1R(pre-oligo-ko) mice had a decreased volume (by 35-55%) and cell number (by 54-70%) in the corpus callosum (CC) and anterior commissure at 2 and 6 weeks of age, respectively. IGF1R(oligo-ko) mice by 25 weeks of age also showed reductions, albeit less marked, in CC volume and cell number. Unlike astrocytes, the percentage of NG2(+) oligodendrocyte precursors was decreased by approximately 13% in 2-week-old IGF1R(pre-oligo-ko) mice, while the percentage of CC1(+) mature oligodendrocytes was decreased by approximately 24% in 6-week-old IGF1R(pre-oligo-ko) mice and approximately 25% in 25-week-old IGF1R(oligo-ko) mice. The reduction in these cells is apparently a result of decreased proliferation and increased apoptosis. These results indicate that IGF-I directly affects oligodendrocytes and myelination in vivo via IGF1R, and that IGF1R signaling in the cells of oligodendrocyte lineage is required for normal oligodendrocyte development and myelination. These data also provide a fundamental basis for developing strategies with the potential to target IGF-IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of demyelinating disorders.

Animals↗
PubMed1999

Positive and negative regulation of the myeloid dendritic cell lineage.

Recent advances have revealed that dendritic cells (DCs) are not a single cell type, but a system of cells that are phenotypically and functionally diverse. DC subtypes stemming from the myeloid and lymphoid lineages promote a diversity of immune responses ranging from the stimulation of naive T and B cell responses to the down-regulation of T cell responses. Although differences in antigen handling are linked to DC developmental stages in the myeloid DC lineage, the particular type of immune response elicited may be determined by a specific DC subtype. This review summarizes key regulatory mechanisms controlling the development of myeloid lineage DCs from multipotent progenitors. Emphasis is placed on describing a highly orchestrated series of proliferative, apoptotic, and developmental events involving granulocyte-macrophage colony-stimulating factor, transforming growth factor beta, and the tumor necrosis factor alpha, CD95, and bcl-2 protein families.

Animals↗
PubMed2000

Regulatory roles for FcgammaRIII (CD16) and FcgammaRII (CD32) in the development of T- and B-lineage lymphoid cells.

IgG Fc receptors (FcgammaR) occur on all hematopoietic lineages and participate in a diversity of functions that reflect the combined effects of the molecular heterogeneity of FcgammaR and the inherent specialization of the FcgammaR+ cells. An extensive literature describes the functions of FcgammaR on mature myeloid and lymphoid cells in humans and mice but little has been published about FcgammaR on lineage progenitor cells. Several studies suggest that FcgammaR can influence leukocyte development and that FcgammaRII (CD32) and FcgammaRIII (CD16) can regulate murine T- and B-lineage development at stages before the expression of clonal antigen receptors. The nominal ligand of FcgammaR is IgG and the physiologically relevant ligand is the IgG-antigen complex, but it is also known that alternative, non-Ig ligands exist for Fc receptors. A role for FcgammaR in the regulation of leukocyte development has potential relevance for clinical situations in which the levels of nominal and/or alternative ligands of FcgammaR are elevated, or the production of soluble forms of FcgammaR is increased.

Animals↗
PubMed2026

Genomic Epidemiology and Clinical Characteristics of Mpox Lineage C.1 Outbreak in Thailand, 2023-2024.

Since 2022, human monkeypox virus (hMPXV) has emerged in non-endemic regions, including Thailand. However, the genomic dynamics and clinical correlates of local transmission remain incompletely defined. Whole-genome sequencing was performed on hMPXV from 16 patients in Thailand (2023-2024) using targeted amplicon NGS. Phylogenetic analyses integrated global reference sequences. Mutational profiles, specifically non-synonymous substitutions and APOBEC3-associated signatures, were analyzed in relation to clinical data. Phylogenetic reconstruction identified three temporal phases. Early 2022 cases (clade IIb lineages A and B) were interspersed with global sequences, consistent with multiple introductions. In contrast, 2023-2024 cases were dominated by lineage C.1. All 16 genomes belonged to C.1 (one C.1.1), and formed a distinct mid-2023 cluster, designated C.1/Thai/Cluster, supporting sustained local transmission. APOBEC3-associated mutations were pervasive across the C.1 lineage overall, including within C.1/Thai/Cluster, without evidence of significant enrichment specific to this cluster. The cohort comprised exclusively male patients (81% HIV-positive, MSM), with predominantly genital painful lesions and a median recovery time of 23 days. No significant associations were detected between viral genetic variation and clinical outcomes. Mpox transmission in Thailand evolved from multiple introductions to sustained C.1-dominated local spread, underscoring the importance of continued genomic surveillance.

Humans↗
PubMed2002

Expression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies.

We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized in live tissue throughout embryonic and postnatal development. Immunohistochemical analysis in brain tissue and in sciatic nerve demonstrated that EGFP expression was restricted to cells of the oligodendrocyte and Schwann cell lineages. EGFP was also strongly expressed in "adult" oligodendrocyte progenitors (OPs) and in gray matter oligodendrocytes. Fluorescence-activated cell sorting allowed high-yield purification of EGFP(+) oligodendrocyte-lineage cells from transgenic brains. Electrophysiological patch clamp recordings of EGFP(+) cells in situ demonstrated that OP cells displayed large outward tetraethylammonium (TEA)-sensitive K(+) currents and very small inward currents, whereas mature oligodendrocytes were characterized by expression of large inward currents and small outward K(+) currents. The proliferation rate of EGFP(+) cells in developing white matter decreased with the age of the animals and was strongly inhibited by TEA. Oligodendrocyte development and physiology can be studied in live tissue of CNP-EGFP transgenic mice, which represent a source of pure EGFP(+) oligodendrocyte-lineage cells throughout development.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2002

A review of inner ear fate maps and cell lineage studies.

A renewed interest in the development of the inner ear has provided more data on the fate and cell lineage relationships of the tissues making up this complex structure. The inner ear develops from a simple ectodermal thickening of the head called the otic placode, which undergoes a great deal of growth and differentiation to form a multichambered nonsensory epithelium that houses the six to nine sensory organs of the inner ear. Despite a large number of studies examining otic development, there have been surprisingly few fate maps generated. The published fate maps encompass four species and range from preotic to otocyst stages. Although some of these studies were consistent with a compartment and boundary model, other studies reveal extensive cell mixing during development. Cell lineage studies have been done in fewer species. At the single cell level the resulting clones in both chicks and frogs appear somewhat restricted in terms of distribution. We conclude that up until late placode stages there are no clear lineage restriction boundaries, meaning that cells seem to mix extensively at these early stages. At late placode stages, when the otic cup has formed, there are at least two boundaries located dorsally in the forming otocyst but none ventrally. These conclusions are consistent with all the fate maps and reconciles the chick and frog data. These results suggest that genes involved in patterning the inner ear may have dynamic and complex expression patterns.

Animals↗
PubMed2004

Association of cytogenetic abnormalities with detection of BCR-ABL fusion transcripts in children with T-lineage lymphoproliferative diseases (T-ALL and T-NHL).

Detection of Philadelphia chromosome (Ph) in childhood T-lineage acute lymphoproliferative disorders is a rare event. Additional cytogenetic abnormalities are particularly uncommon in ALL. We here report two cases with T lineage acute lymphoproliferative disorders (T-ALL and T-NHL) presenting with both cytogenetic alterations and BCR-ABL fusion transcripts, associated with an aggressive presentation and a poor outcome. We point out firstly on the cytogenetic aberrations, supporting the hypothesis of multi-lineage involvement of ALL expressing Ph chromosome; secondly, on the persistence of T-cell leukemic clone detected by minimal residual disease (MRD) analysis, despite of the early disappearance of BCR-ABL fusion transcript.

Adolescent↗
PubMed1996

Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages.

The cellular and molecular processes leading to the establishment of the skeletal muscle lineage in the vertebrate are not well understood. The MyoD-related family of myogenic regulatory factors (MRFs) are expressed during somitogenesis although cells with myogenic capacity are present prior to gastrulation. We propose that regulatory genes exist that guide the skeletal muscle lineage during early development. In an effort to identify these regulatory genes, we performed a differential screening to isolate transcripts that are present in myogenic cells and in the embryo prior to MRF expression but absent in nonmyogenic fibroblasts. We report here the identification of Pw1. The Pw1 transcript is approximately 8.5 kb long and encodes a large protein containing 12 widespread C2H2 zinc fingers and 3 motifs containing periodic prolines and acidic residues. Consistent with the possibility that Pw1 is a transcription factor, we observe nuclear localization of the protein. Pw1 is strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the central nervous system. Pw1 is initially expressed in all mesodermal cells early in development; however, its maintained expression in adult differentiated muscle suggests a specific role in the skeletal muscle lineage. Pw1 expression is cell cycle specific with levels highest during late M-phase. The gene is intronless which may facilitate transcription during cell division. At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures.

Animals↗
PubMed1997

Soma-germ cell interactions in Caenorhabditis elegans: multiple events of hermaphrodite germline development require the somatic sheath and spermathecal lineages.

Germ cells complete multiple events to form functional oocytes and sperm. In the Caenorhabditis elegans hermaphrodite, germ cells develop in proximity to the somatic gonad sheath and spermathecal cells. We present evidence from cellular laser ablation studies indicating that cells of the somatic sheath and spermathecal lineages play critical roles in four events of hermaphrodite germline development. (1) Cells of the sheath and spermathecal lineage support germline proliferation; ablation of sheath/spermathecal precursor cells reduces mitotic proliferation. (2) These cells also play a role in the exit of germ cells from the pachytene stage of meiotic prophase and/or gamete differentiation; ablation can result in undifferentiated germ cells arrested in pachytene. (3) Proximal sheath and distal spermatheca cells are required for ovulation of the oocyte. During wild-type ovulation, the mature oocyte is expelled from the gonad arm by contraction of the proximal myoepithelial sheath and dilation of the distal spermatheca. Ablation of these cells traps mature oocytes in the gonad arm where they endomitotically replicate their DNA (the Emo phenotype). (4) Cells of the sheath and spermathecal lineage also appear to promote the male germ cell fate since ablation of one sheath/spermathecal precursor cell can feminize the hermaphrodite germ line. These somatic ablation-induced germline phenotypes demonstrate that the somatic gonad is required for multiple events in C. elegans germline development. Further, these results suggest that soma to germline cell-cell interactions in C. elegans are physiological in character (i.e., contraction during ovulation) as well as regulatory.

Animals↗
PubMed2001

Neurons and glia in the midline of the higher crustacean Orchestia cavimana are generated via an invariant cell lineage that comprises a median neuroblast and glial progenitors.

Midline cells are a common feature of both insects and crustaceans. Midline cells in the insects Schistocerca americana and Drosophila melanogaster have been shown to give rise to pairs of either neurons or glial cells (midline precursor) as well as to repeatedly generate neurons (median neuroblast) or both neurons and glia (median neuroglioblast). This study addresses midline cell lineages in a higher crustacean, the amphipod Orchestia cavimana. In vivo labeling of single midline cells shows that the resulting cell lineage is invariant and that these cells act as progenitors for sets of three glial precursors and one median neuroblast. The progeny are restricted to parasegmental units. The glial precursors give rise to three pairs of glial cells; two of them enwrap the commissures. The median neuroblast gives rise to about 10 cells that differentiate into 3 classes of neurons. The presence of median neuroblasts is also shown for another higher crustacean, the isopod Porcellio scaber using BrdU labeling. This is the first study to analyze the cell lineage of crustacean neurons generated by early ectodermal precursors. A comparison with those of insects demonstrates both conservation and change during the evolution of arthropods.

Animals↗
PubMed2002

Cell lineage dynamics in stratified shoot apical meristems.

We devise a stochastic and spatially explicit model for the dynamics of the initials cells in a stratified shoot apical meristem (SAM). The meristem is composed of three layers with seven initials per layer. We investigate the probability and number of divisions for a mutant lineage to either reach fixation or becoming purged through selection or drift. In contrast to previous studies our results show that the functional organization of the initials in stratified SAMs acts as an efficient purging mechanism particularly of deleterious mutations. All mutants are rapidly purged when deleterious. The probability of fixation for mutants with a higher fitness than the wild type increases linearly up to 70%. The median number of divisions to fixation of both genotypes is insensitive to the mutant's fitness. The median number of divisions to wild-type fixation is less than 100, with the upper quartile below 200. The largest number of divisions to wild-type fixation are in the order of 100 000 divisions. Our results indicate that the spatial organization of SAM enables the efficient purging of mutant lineages, particularly if they are deleterious. On the other hand, long-lived chimeric stages are common when mutant lineages succeed to overcome the initial numerical disadvantage.

Cell Division↗
PubMed1996

Regulation of FGF receptors in the oligodendrocyte lineage.

Fibroblast growth factors (FGFs) affect a broad spectrum of developmentally regulated cellular responses involved in the control of growth and differentiation. To identify specific FGF receptor forms involved in these responses, we have characterized FGF receptor transcript expression, and its modulation by FGF-2, as enriched populations of oligodendrocyte progenitors differentiate into mature oligodendrocytes. The data demonstrate that the levels of mRNA expression for FGF high-affinity receptors-1, -2, and -3 are differentially regulated during lineage progression: FGF receptor-1 expression increases with lineage progression, FGF receptor-2 is predominantly expressed by terminally differentiated oligodendrocytes, and FGF receptor-3 reaches a peak level of expression in late progenitors and then declines upon further differentiation; FGF receptor-4 expression was not detected in oligodendrocytes. Distinct patterns of alternatively spliced variants of FGF receptor-1 and -2 transcripts are expressed: the predominant FGF receptor-1 transcripts contain three Ig-like domains (FGF receptor-1 alpha), whereas the FGF receptor-2 transcripts contain two Ig-like domains (FGF receptor-2 beta 2) and this form is up-regulated as oligodendrocytes differentiate. In addition, the expression of these receptors is differentially regulated by the ligand, FGF-2: FGF receptor-1 mRNA expression is up-regulated in early progenitors, and FGF receptor-2 mRNA expression is down-regulated in mature oligodendrocytes. Finally, astrocytes express FGF receptor-1, -2, and -3 transcripts, but at different levels and with different exon utilization (FGF receptor-1 beta, FGF receptor-2 beta 1/beta 2) compared to oligodendrocytes. To our knowledge this is the first report that demonstrates that the mRNA expression of these three FGF receptor types is differentially regulated in primary cells as they differentiate along a lineage from progenitors to terminally differentiated cells. We propose that this pattern of expression provides a molecular basis for the developmentally varying response of cells to a common ligand. For example, according to this hypothesis, in response to FGF-2, FGF receptor-1 transduces signals that stimulate the prolonged proliferation and migration of early progenitors, FGF receptor-3 promotes the proliferation and arrest of differentiation of late progenitors, and FGF receptor-2 transduces signals for terminal differentiation, but not proliferation, in mature oligodendrocytes.

Alternative Splicing↗
PubMed1999

Signals involved in CD4/CD8 lineage commitment: current concepts and potential mechanisms.

A competent immune system requires that mature T cells express TCR and CD4/CD8 coreceptors with matching MHC specificities. Such matching of TCR and coreceptor specificity is induced in the thymus at the CD4(+)8(+)stage of development and is referred to as lineage commitment. The process by which immature CD4(+)8(+)thymocytes are signaled to undergo lineage commitment continues to be the subject of intense investigation and discussion. Here, we review the major models by which lineage commitment is thought to occur and discuss the experimental results on which they were based.

Animals↗
PubMed2006

Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota.

The evolutionary origin of "orphan" genes, genes that lack sequence similarity to any known gene, remains a mystery. One suggestion has been that most orphan genes evolve rapidly so that similarity to other genes cannot be traced after a certain evolutionary distance. This can be tested by examining the divergence rates of genes with different degrees of lineage specificity. Here the lineage specificity (LS) of a gene describes the phylogenetic distribution of that gene's orthologues in related species. Highly lineage-specific genes will be distributed in fewer species in a phylogeny. In this study, we have used the complete genomes of seven ascomycotan fungi and two animals to define several levels of LS, such as Eukaryotes-core, Ascomycota-core, Euascomycetes-specific, Hemiascomycetes-specific, Aspergillus-specific, and Saccharomyces-specific. We compare the rates of gene evolution in groups of higher LS to those in groups with lower LS. Molecular evolutionary analyses indicate an increase in nonsynonymous nucleotide substitution rates in genes with higher LS. Several analyses suggest that LS is correlated with the evolutionary rate of the gene. This correlation is stronger than those of a number of other factors that have been proposed as predictors of a gene's evolutionary rate, including the expression level of genes, gene essentiality or dispensability, and the number of protein-protein interactions. The accelerated evolutionary rates of genes with higher LS may reflect the influence of selection and adaptive divergence during the emergence of orphan genes. These analyses suggest that accelerated rates of gene evolution may be responsible for the emergence of apparently orphan genes.

Ascomycota↗
PubMed2000

Telomere-associated RFLPs and electrophoretic karyotyping reveal lineage relationships among race-specific strains of Ustilago hordei.

The inheritance of telomere-associated restriction fragment length polymorphisms (tel-RFLP) and chromosome-length polymorphisms (CLPs) were criteria used for the identification of strains of Ustilago hordei that form a direct lineage. Teliospore collections of race 8 strains and strains reported to be derived from race 8 through inbreeding were used in these analyses. None of the race 8 strains examined in this study, representing three consecutive inbred generations, was polymorphic for any terminal BamHI and BglII chromosomal loci, nor did they have any apparent CLPs. Strains from a teliospore collection obtained in 1971 and designated 447, representing the first inbred generation of race 8 strains and a shift to increased virulence on cultivar Hannchen, had tel-RFLP arrays indistinguishable from the race 8 strains isolated in this study; and they had no obvious CLPs. Strains from the presumed second inbred generation, the 1279 teliospore line, which was pathogenic on six additional cultivars, had numerous CLPs and a tel-RFLP array that differed from race 8 strains at more than 50% of the terminal chromosomal BamHI and BglII restriction sites. The tel-RFLP array of each 1279 strain was identical and indistinguishable from the arrays of strains representing races 10 and 13, indicating that they share a direct lineage. A race 14 strain, also presumed to be derived from race 8 strains by inbreeding, had a unique tel-RFLP array and an electrophoretic karyotype that distinguished it from all other strains. The tel-RFLP arrays alone eliminate the 1279 and race 14 strains from being direct descendants from race 8 strains by inbreeding and suggest that this approach can identify a strain lineage among other inbred sexually reproducing fungi, or isolates that comprise different asexual clonal populations.

Blotting, Southern↗
PubMed2004

Evolution of the larval peripheral nervous system in Drosophila species has involved a change in sensory cell lineage.

A key challenge in evolutionary biology is to identify developmental events responsible for morphological changes. To determine the cellular basis that underlies changes in the larval peripheral nervous system (PNS) of flies, we first described the PNS pattern of the abdominal segments A1-A7 in late embryos of several fly species using antibody staining. In contrast to the many variations reported previously for the adult PNS pattern, we found that the larval PNS pattern has remained very stable during evolution. Indeed, our observation that most of the analysed Drosophilinae species exhibit exactly the same pattern as Drosophila melanogaster reveals that the pattern observed in D. melanogaster embryos has remained constant for at least 40 million years. Furthermore, we observed that the PNS pattern in more distantly related flies (Calliphoridae and Phoridae) is only slightly different from the one in D. melanogaster. A single difference relative to D. melanogaster was identified in the PNS pattern of the Drosophilinae fly D. busckii, the absence of a specific external sensory organ. Our analysis of sensory organ development in D. busckii suggests that this specific loss resulted from a transformation in cell lineage, from a multidendritic-neuron-external-sensory-organ lineage to a multidendritic-neuron-solo lineage.

Animals↗