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Results for “spatial gene expression”

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At least 91 records · Page 5Linked to original sources
PubMed2004

Adenovirus vectors targeting alphaV integrin or heparan sulfate receptors display different distribution of transgene activity after intramuscular injection.

BACKGROUND: Modification of the fiber proteins in replication-deficient adenoviral (Ad) vectors through incorporation of specific receptor-binding motifs may represent a strategy to enhance their tissue targeting capabilities. METHODS: In this study, we compared an unmodified Ad (GV10) with two mutated vectors obtained by insertion of specific target sequences that redirect binding, either toward alpha(V) integrin (RGD) or heparan sulfate (UTV) cellular receptors, for reporter gene expression spatial distribution in the rabbit skeletal muscle. In a first series of experiments, injection volume was kept constant and activity of a lacZ transgene was evaluated 48 h after injection of the Ad vectors at different doses. In separate experiments, the effects of different volumes of injection at a constant dose of Ad vector were monitored. RESULTS: All vectors evaluated showed a significant increase in the number of lacZ-positive muscle segments, with increasing vector dose. However, in muscles treated with the UTV vector, fewer muscle fibers were beta-gal-positive than in GV10 or RGD vector treated animals. In fact, total beta-gal activity increased in a dose-dependent fashion in the GV10- and RGD-treated muscles, but not in the UTV-treated ones. Remarkably, in samples from UTV-treated animals, a volume-dependent enhancement of transgene expression was observed during experiments performed at the same dose and different injection volumes. CONCLUSIONS: The results of the present study demonstrate that altering Ad affinity for cellular receptors modulates the level and distribution of transgene activity, conferring characteristics that may allow for treatment customization.

Adenoviridae↗
PubMed1999

Green fluorescent protein as a reporter for spatial and temporal gene expression in Streptomyces coelicolor A3(2).

The enhanced green fluorescent protein (EGFP) gene is a modified version of the green fluorescent protein gene of the jellyfish Aequorea victoria with a codon usage that corresponds well to that found in many GC-rich streptomycete genes. Here the use of EGFP as a reporter for the analysis of spatially and temporally regulated gene expression in Streptomyces coelicolor A3(2) is demonstrated. The EGFP gene was inserted into plasmids that can replicate in Escherichia coli, greatly facilitating the construction of EGFP gene fusions. The plasmids can be transferred readily to S. coelicolor by conjugation, whereupon two of them (pIJ8630 and pIJ8660) integrate at the chromosomal attachment site for the temperate phage phiC31. These vectors were used to analyse the spatial and temporal expression of sigF, which encodes a sigma factor required for spore maturation, and of redD, a pathway-specific regulatory gene for the production of undecylprodigiosin, one of the four antibiotics made by S. coelicolor. While transcription of sigF appeared to be confined to developing and mature spore chains, transcription of redD occurred only in ageing substrate mycelium. A further plasmid derivative (pIJ8668) was made that lacks the phiC31 attachment site, allowing the EGFP gene to be fused transcriptionally to genes of interest at their native chromosomal locations.

Bacterial Proteins↗
PubMedDate not supplied

Calbindin D-28K immunoreactivity of human cone cells varies with retinal position.

Calbindin D-28K is a calcium-binding protein found in the cone but not rod photoreceptor cells in the retinas of a variety of species. Recent studies of the monkey retina indicated that calbindin D-28K may be expressed preferentially in non-foveal regions of the retina. In the current studies of human retinas, immunohistochemical experiments demonstrated that calbindin D-28K is reduced or absent in the fovea and parafovea, but prevalent in the perifovea and periphery. These findings were supported by the quantification of calbindin D-28K in 1-mm trephine punches obtained from different regions of the human retina. The specificity of the anti-calbindin D-28K antibodies used in these studies was confirmed by Western blot analysis using purified calbindin D-28K. The protein was purified from retinal tissue and its identity confirmed by partial amino-acid sequence analysis. The expression of calbindin D-28K did not correlate with the spectral properties of the cones, rather to their position in the retina. The study of spatially expressed genes, like the one encoding calbindin D-28K, may help explain the patterns of retinal degeneration seen in some human cone-rod dystrophies.

Aged↗
PubMed2003

Epigenetic reprogramming in mammalian nuclear transfer.

With the exception of lymphocytes, the various cell types in a higher multicellular organism have basically an identical genotype but are functionally and morphologically different. This is due to tissue-specific, temporal, and spatial gene expression patterns which are controlled by genetic and epigenetic mechanisms. Successful cloning of mammals by transfer of nuclei from differentiated tissues into enucleated oocytes demonstrates that these genetic and epigenetic programs can be largely reversed and that cellular totipotency can be restored. Although these experiments indicate an enormous plasticity of nuclei from differentiated tissues, somatic cloning is a rather inefficient and unpredictable process, and a plethora of anomalies have been described in cloned embryos, fetuses, and offspring. Accumulating evidence indicates that incomplete or inappropriate epigenetic reprogramming of donor nuclei is likely to be the primary cause of failures in nuclear transfer. In this review, we discuss the roles of various epigenetic mechanisms, including DNA methylation, chromatin remodeling, imprinting, X chromosome inactivation, telomere maintenance, and epigenetic inheritance in normal embryonic development and in the observed abnormalities in clones from different species. Nuclear transfer represents an invaluable tool to experimentally address fundamental questions related to epigenetic reprogramming. Understanding the dynamics and mechanisms underlying epigenetic control will help us solve problems inherent in nuclear transfer technology and enable many applications, including the modulation of cellular plasticity for human cell therapies.

Animals↗
PubMed1995

Measurement of mRNA levels in tumor xenografts with quantitative autoradiography and in situ hybridization.

In situ methodologies allow qualitative and semi-quantitative analysis of spatial gene expression in whole organisms or tissues. We have applied quantitative autoradiography to in situ hybridizations of sections from human breast tumor xenografts to measure mRNA levels for ornithine decarboxylase, estrogen receptor, transforming growth factor alpha, and glyceraldehyde-3-phosphate dehydrogenase. Comparisons of control and tamoxifen-treated animals show significant decreases in MCF-7 tumor estrogen receptor mRNA levels in the drug-treated animals. Combining quantitative autoradiography with in situ hybridization allows measurement of absolute rather than relative mRNA levels for genes of interest, and to monitor effector-induced changes in these mRNAs in vivo.

Animals↗
PubMed2025

SpaceBar enables clone tracing in spatial transcriptomic data.

We report a cellular barcoding strategy, SpaceBar, that enables simultaneous clone tracing and spatial transcriptomics profiling. Our approach uses a library of 96 synthetic barcode sequences that can be robustly detected by imaging based spatial transcriptomics (seqFISH), delivered such that each cell is labeled with a combination of barcodes. We used these barcodes to label melanoma cells in a tumor xenograft model and profiled both clone identity and spatial gene expression in situ. We developed a gene scoring metric that quantifies how strongly gene expression is driven by intrinsic cellular cues or extrinsic environmental signals. Our framework distinguishes between clonal dynamics and environmentally-driven transcriptional regulation in complex tissue contexts.

Journal Article↗
PubMed1994

Pistil-Specific and Ethylene-Regulated Expression of 1-Aminocyclopropane-1-Carboxylate Oxidase Genes in Petunia Flowers.

The differential expression of the petunia 1-aminocyclopropane-1-carboxylate (ACC) oxidase gene family during flower development and senescence was investigated. ACC oxidase catalyzes the conversion of ACC to ethylene. The increase in ethylene production by petunia corollas during senescence was preceded by increased ACC oxidase mRNA and enzyme activity. Treatment of flowers with ethylene led to an increase in ethylene production, ACC oxidase mRNA, and ACC oxidase activity in corollas. In contrast, leaves did not exhibit increased ethylene production or ACC oxidase expression in response to ethylene. Gene-specific probes revealed that the ACO1 gene was expressed specifically in senescing corollas and in other floral organs following exposure to ethylene. The ACO3 and ACO4 genes were specifically expressed in developing pistil tissue. In situ hybridization experiments revealed that ACC oxidase mRNAs were specifically localized to the secretory cells of the stigma and the connective tissue of the receptacle, including the nectaries. Treatment of flower buds with ethylene led to patterns of ACC oxidase gene expression spatially distinct from the patterns observed during development. The timing and tissue specificity of ACC oxidase expression during pistil development were paralleled by physiological processes associated with reproduction, including nectar secretion, accumulation of stigmatic exudate, and development of the self-incompatible response.

Journal Article↗
PubMed2004

Robust identification of large genetic networks.

Temporal and spatial gene expression, together with the concentration of proteins and metabolites, is tightly controlled in the cell. This is possible thanks to complex regulatory networks between these different elements. The identification of these networks would be extremely valuable. We developed a novel algorithm to identify a large genetic network, as a set of linear differential equations, starting from measurements of gene expression at steady state following transcriptional perturbations. Experimentally, it is possible to overexpress each of the genes in the network using an episomal expression plasmid and measure the change in mRNA concentration of all the genes, following the perturbation. Computationally, we reduced the identification problem to a multiple linear regression, assuming that the network is sparse. We implemented a heuristic search method in order to apply the algorithm to large networks. The algorithm can correctly identify the network, even in the presence of large noise in the data, and can be used to predict the genes that directly mediate the action of a compound. Our novel approach is experimentally feasible and it is readily applicable to large genetic networks.

Algorithms↗
PubMed2001

Transcriptional dysregulation in skeletal malformation syndromes.

Normal skeletal development requires coordinated temporal and spatial gene expression patterns that specify the functions of various cell types. Transcription factors by definition coordinate this process and are themselves subject to hierarchical levels of regulation. Together they determine the context-dependent function of each transcription factor. Hence, loss-of-function and gain-of-function mutations within specific transcription factors cause dysregulation of broad transcriptional networks. Consequences are usually dominantly inherited skeletal malformation syndromes that can be broadly viewed as consequences of defects of cellular differentiation, proliferation, and survival versus defects in pattern formation. The study of human phenotypes and mutations can lead to hypotheses about targets within the respective transcriptional network. These targets can then be confirmed by combining mouse genetic and in vitro studies. Although this has been successful in a small group of skeletal dysplasias, the majority of transcriptional networks during skeletogenesis remain to be elucidated.

Acrocephalosyndactylia↗
PubMed1995

Temporal and spatial patterns of gene expression for the hatching enzyme in the teleost embryo, Oryzias latipes.

The hatching enzyme of the medaka, Oryzias latipes, consists of two proteases, high choriolytic enzyme (HCE) and low choriolytic enzyme (LCE). They are synthesized and accumulated in the same unicellular hatching glands and are secreted from them at the end of embryonic development to digest the egg envelope. Recently, these enzymes were purified, and their cDNA clones were isolated. In the present study, we examined temporal and spatial patterns of expression of the hatching enzyme genes during embryogenesis using cDNAs for HCE and LCE as probes. According to Northern blotting analysis, the expression of both genes started at the same time (stage 21-22 embryos: brain differentiation and lens formation) and the patterns of expression changed in parallel during development. In situ hybridization to whole embryo and the sections revealed that the expression of the HCE genes was detected first in the anterior end of the hypoblast layer in stage 16-17 (late gastrula) embryos. Distinct signals of the HCE gene expression were then detected in a group of cells located at the front of the head rudiment of embryos at stage 18-19 (1 somite). Treatment of the embryos with retinoic acid, which is known to affect the anterior differentiation of embryos, suppressed the hatching gland cell differentiation in accordance with the result of in situ hybridization. In stage 22 embryos, the HCE-positive cells dispersed in an ectodermal layer under the forebrain and optic vesicles. Thereafter, the hatching gland cells expressing the HCE mRNA were aligned along the branchial arches and finally rearranged to the inner wall of the pharyngeal cavity, following a marked elongation of the lower jaw. The results of in situ hybridization to whole embryos at consecutive developmental stages demonstrated that the hatching gland cells located at the most anterior portion of the hypoblast migrated posteriorward to endoderm (pharyngeal endoderm) by way of ectoderm, while they were expressing mRNA for the hatching enzyme. Retinoic acid treatment of embryos gave rise to aberrations in the final location of the hatching gland cells probably by disturbing their migration. Moreover, the number of hatching gland cells increased markedly during their migration. This fact strongly suggested a concurrence of gene expression and mitosis of a gland cell and/or a successive initiation of gene expression in maturing gland cells during migration.

Animals↗
PubMed1987

Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis.

The gooseberry (gsb) locus contains two closely linked genes, BSH9 and BSH4, which are structurally related to each other and to the paired (prd) gene. Sequence analysis of genomic DNA and cDNA shows that BSH9 and BSH4 can encode proteins of 427 and 452 amino acids, respectively. The structural homology between these two putative proteins and the prd protein consists essentially of two domains forming most of the amino-terminal halves of the proteins: the prd domain of 128 amino acids and a prd-type homeo domain of 60 amino acids, which is extended by 18 amino acids at its amino-terminal end. The temporal profiles of BSH9 and BSH4 transcripts, as characterized by Northern analysis, show a peak shortly after the peak of prd transcripts. The spatial distributions of BSH9 and BSH4 transcripts have been analyzed by in situ hybridization to whole-mount and sectioned embryos. BSH9 transcripts appear in the posterior ventrolateral part of each primordial segment throughout the embryo, including head and tail segments. Transcripts are initially restricted to the ectoderm, in which they arise as two spatially shifted and temporally delayed waves exhibiting double-segment periodicity and anteroposterior polarity. During germ-band extension, BSH9 is induced in the mesoderm in register with the ectoderm and neurectoderm and in the tail segments A9-A11. In contrast, BSH4 transcripts appear with a single-segment repeat, first, in the neurectoderm during germ-band extension and, later, in single neurons during neuronal differentiation. BSH9, BSH4, and prd are activated in cells that are in register along the anteroposterior axis of the embryo in the posterior parts of primordial segments comprising the posterior compartments of engrailed expression.

Age Factors↗
PubMed1995

Homeobox-containing gene transiently expressed in a spatially restricted pattern in the early sea urchin embryo.

In the sea urchin embryo, the lineage founder cells whose polyclonal progenies will give rise to five different territories are segregated at the sixth division. To investigate the mechanisms by which the fates of embryonic cells are first established, we looked for temporal and spatial expression of homeobox genes in the very early cleavage embryos. We report evidence that PlHbox12, a paired homeobox-containing gene, is expressed in the embryo from the 4-cell stage. The abundance of the transcripts reaches its maximum when the embryo has been divided into the five polyclonal territories--namely at the 64-cell stage--and it abruptly declines at later stages of development. Blastomere dissociation experiments indicate that maximal expression of PlHbox12 is dependent on intercellular interactions, thus suggesting that signal transduction mechanisms are responsible for its transcriptional activation in the early cleavage embryo. Spatial expression of PlHbox12 was determined by whole-mount in situ hybridization. PlHbox12 transcripts in embryos at the fourth, fifth, and sixth divisions seem to be restricted to the conditionally specified ectodermal lineages. These results suggest a possible role of the PlHbox12 gene in the early events of cell specification of the presumptive ectodermal territories.

Amino Acid Sequence↗
PubMed1990

Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos.

During Drosophila embryogenesis homeotic genes control the developmental diversification of body structures. The genes probably coordinate the expression of as yet unidentified target genes that carry out cell differentiation processes. At least four homeotic genes expressed in the visceral mesoderm are required for midgut morphogenesis. In addition, two growth factor homologs are expressed in specific regions of the visceral mesoderm surrounding the midgut epithelium. One of these, decapentaplegic (dpp), is a member of the transforming growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of the mammalian proto-oncogene int-1. Here we show that the spatially restricted expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp. One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells. In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells. The two growth factor genes therefore are excellent candidates for target genes that are directly regulated by the homeotic genes.

Animals↗
PubMed2001

Spatial and temporal collagen gene expression in lumbar intertransverse fusion in the rabbit.

We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-alpha1 (I) collagen (COL1A1), pro-alpha1 (II) collagen (COL2A1) and pro-alphal (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COLlA1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion.

Animals↗
PubMed1993

The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos.

The pattern of RNA expression of the murine Dlx-2 (Tes-1) homeobox gene is described in embryos ranging in age from E8.5 through E11.5. Dlx-2 is a vertebrate homologue of the Drosophila Distal-less (Dll) gene. Dll expression in the Drosophila embryo is principally limited to the primordia of the brain, head and limbs. Dlx-2 is also expressed principally in the primordia of the forebrain, head and limbs. Within these regions it is expressed in spatially restricted domains. These include two discontinuous regions of the forebrain (basal telencephalon and ventral diencephalon), the branchial arches, facial ectoderm, cranial ganglia and limb ectoderm. Several mouse and human disorders have phenotypes which potentially are the result of mutations in the Dlx genes.

Animals↗
PubMed2005

Spatial diversity in gene expression for VDCCgamma subunit family in developing and adult mouse brains.

The gamma subunit of voltage-dependent Ca2+ channels (VDCCs) is characterized by molecular diversity and regulation of AMPA-type glutamate receptors as well as VDCCs. In the present study, we examined expressions for the VDCCgamma1-8 subunit mRNAs in developing and adult mouse brains by in situ hybridization. In adult brains, the gamma2 and gamma7 subunit mRNAs were widely expressed in various grey matter regions with the highest level in cerebellar Purkinje cells and granule cells. The gamma3 and gamma8 subunit mRNAs predominated in the telencephalon, with the latter being at striking levels in the hippocampus. The gamma4 subunit mRNA was enriched in the olfactory bulb, striatum, thalamus and hypothalamus. The gamma5 subunit mRNA was abundant in the olfactory bulb, hippocampal CA2, thalamus, inferior colliculus and Bergmann glia. Transcripts of these subunits were detected in embryonic brains: some showed well-preserved spatial patterns (gamma2, gamma5, gamma7 and gamma8), while others underwent developmental up- (gamma3) or down-regulation (gamma4). In contrast, the gamma1 and gamma6 subunit mRNAs were negative or very low throughout brain development. Therefore, the present study has revealed spatial diversity in gene expression for individual VDCCgamma subunits, presumably reflecting functional diversity of this protein family and their differential involvement in neural function.

Animals↗
PubMed2025

tomoseqr: A Bioconductor package for spatial reconstruction and visualization of 3D gene expression patterns based on RNA tomography.

RNA tomography computationally reconstructs 3D spatial gene expression patterns genome-widely from 1D tomo-seq data, generated by RNA sequencing of cryosection samples along three orthogonal axes. We developed tomoseqr, an R package designed for RNA tomography analysis of tomo-seq data, to reconstruct and visualize 3D gene expression patterns through user-friendly graphical interfaces. We show the effectiveness of tomoseqr using simulated and real tomo-seq data, validating its utility for researchers. R package tomoseqr is available on Bioconductor (https://doi.org/doi:10.18129/B9.bioc.tomoseqr) and GitHub (https://github.com/bioinfo-tsukuba/tomoseqr).

Software↗
PubMed2005

Systematic spatial analysis of gene expression during wheat caryopsis development.

The cereal caryopsis is a complex tissue in which maternal and endosperm tissues follow distinct but coordinated developmental programs. Because of the hexaploid genome in wheat (Triticum aestivum), the identification of genes involved in key developmental processes by genetic approaches has been difficult. To bypass this limitation, we surveyed 888 genes that are expressed during caryopsis development using a novel high-throughput mRNA in situ hybridization method. This survey revealed novel distinct spatial expression patterns that either reflected the ontogeny of the developing caryopsis or indicated specialized cellular functions. We have identified both known and novel genes whose expression is cell cycle-dependent. We have identified the crease region as important in setting up the developmental patterning, because the transition from proliferation to differentiation spreads from this region to the rest of the endosperm. A comparison of this set of genes with the rice (Oryza sativa) genome shows that approximately two-thirds have rice counterparts but also suggests considerable divergence with regard to proteins involved in grain filling. We found that the wheat genes had significant homology with 350 Arabidopsis thaliana genes. At least 25 of these are already known to be essential for seed development in Arabidopsis, but many others remain to be characterized.

Cell Cycle↗