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Results for “spatial gene expression”

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At least 631 records · Page 35Linked to original sources
PubMed1999

Pax-6 interactions with TATA-box-binding protein and retinoblastoma protein.

PURPOSE: To identify proteins that physically interact with Pax-6, a paired domain- and homeodomain (HD)-containing transcription factor that is a key regulator of eye development. METHODS: Protein-protein interactions involving Pax-6, TATA-box-binding protein (TPB), and retinoblastoma protein were studied using affinity chromatography with Pax-6 as ligand, glutathione-S-transferase (GST) pull-down assays, and immunoprecipitations. RESULTS: The authors have shown that Pax-6 is a sequence-specific activator of many crystallin genes, all containing a TATA box, in the lens. Others have shown that lens fiber cell differentiation, characterized by temporally and spatially regulated crystallin gene expression, depends on retinoblastoma protein. In the present study it was shown that Pax-6 interacted with the TBP, the DNA-binding subunit of general transcription complex TFIID. GST pull-down assays indicated that this interaction was mediated by the Pax-6 HD, with a substantial role for its N-terminal arm and first two alpha-helices. The experiments also indicated a binding role for the C-terminal-activation domain of the protein. In addition, the present study showed that the HD of Pax-6 interacted with retinoblastoma protein. Immunoprecipitation experiments confirmed retinoblastoma protein/Pax-6 complexes in lens nuclear extracts. CONCLUSIONS: Blending the present results with those in the literature suggests that Pax-6 and retinoblastoma protein participate in overlapping regulatory pathways controlling epithelial cell division, fiber cell elongation, and crystallin gene expression during lens development.

Amino Acid Sequence↗
PubMed2001

Three cryptochromes are rhythmically expressed in Xenopus laevis retinal photoreceptors.

PURPOSE: To clone Xenopus laevis cryptochromes (crys) and to understand their role in the Xenopus retinal clock. METHODS: We designed degenerate PCR primers based on homology between mouse and human crys. DNA fragments generated from these PCR reactions were used to screen a Xenopus retinal cDNA library. Three independent clones were identified and sequenced. The temporal and spatial expression of these genes in retina were studied by Northern blot analysis and in situ hybridization. RESULTS: We cloned three cry homologs from Xenopus laevis retina. We named them xcry1, xcry2a, and xcry2b based on their high homology to the mouse crys. Sequence analysis shows that these Xenopus CRYs have more than 85% identity to mouse CRYs at the amino acid level. Northern blot analysis demonstrated that all three xcrys are rhythmically expressed in the retina with peaks at different times of the day. The xcrys are expressed in a variety of tissues. In retina, they are expressed predominantly in photoreceptor cells. CONCLUSIONS: Our finding of cry expression in Xenopus photoreceptor cells further supports the idea of independent circadian oscillators being present in these cells. The sequence similarities to mouse crys suggest similar functions in the circadian clock. However, their distinct temporal expression patterns suggest some unique role for xCRY in the Xenopus retina.

Amino Acid Sequence↗
PubMed2003

Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion.

The emergence of complex patterns of organization close to the Cambrian boundary is known to have happened over a (geologically) short period of time. It involved the rapid diversification of body plans and stands as one of the major transitions in evolution. How it took place is a controversial issue. Here we explore this problem by considering a simple model of pattern formation in multicellular organisms. By modeling gene network-based morphogenesis and its evolution through adaptive walks, we explore the question of how combinatorial explosions might have been actually involved in the Cambrian event. Here we show that a small amount of genetic complexity including both gene regulation and cell-cell signaling allows one to generate an extraordinary repertoire of stable spatial patterns of gene expression compatible with observed anteroposterior patterns in early development of metazoans. The consequences for the understanding of the tempo and mode of the Cambrian event are outlined.

Adaptation, Physiological↗
PubMedDate not supplied

Spore formation in Bacillus subtilis.

Bacillus subtilis is the best studied of the bacteria that make heat-resistant spores in response to starvation. The process of sporulation results in the formation of a cell type which is quite different in morphology from that of bacteria during normal growth. Sporulation requires the activation, in an ordered sequence, of many genes that are kept silent during vegetative growth. It also requires that these genes be activated differentially in two sister cells that are genetically identical. The sophisticated mechanisms responsible for both the temporal and the spatial regulation of gene expression are now understood in a fair amount of detail. They are likely to provide models which will make a valuable contribution to studies of development and differentiation in higher cells.

Bacillus subtilis↗
PubMed1997

Tissue specific control regions of the N-methyl-D-aspartate receptor subunit NR2C promoter.

In the mouse brain, the N-methyl-D-aspartate receptor subunit NR2C (epsilon-3) is mainly detected in the cerebellar granule cells starting from the second week of postnatal life. In order to improve our understanding of molecular mechanisms of this neuron-specific, spatial and temporal gene expression, different promoter fragments were used to control indicator genes in nondifferentiated rat pheochromocytoma (PC12) cells, in human embryonal kidney (HEK293) cells and in transgenic mice. A 400 bp NR2C promoter region upstream of the transcriptional start site was identified as a basal promoter that was negatively regulated possibly by a neuron restrictive silencer element (NRSE) that is localized 664 base pairs downstream from the transcriptional start sites.

Animals↗
PubMed1998

Regulation of the Caenorhabditis elegans gut cysteine protease gene cpr-1: requirement for GATA motifs.

Expression of the Caenorhabditis elegans cysteine protease gene cpr-1 is regulated both spatially and temporally. In situ hybridisation and Northern blot analysis have shown that this gene is expressed exclusively in gut cells of all developmental stages except the embryo. We now show by transgenic transformation with cpr-1/lac Z reporter gene constructs that a sequence contained within the cpr-1 5' flanking region can direct this spatial and temporal expression. Deletion analysis of the cpr-1 promoter indicates that as little as 212 bp of upstream sequence is sufficient for this expression, although more upstream sequence may be involved in quantitative regulation of expression. Mutation of two GATA-like sequence elements at positions -51 and -147 upstream of the transcription start site ablates all expression, indicating an essential role in cpr-1 regulation. A concatemer of the cpr-1 -147 GATA motif placed upstream of minimal promoter/lac Z reporter gene constructs results in strong reporter gene expression in gut cells of larval stages and also in embryos. Weak expression is also detected in hypodermal cells. This pattern is reversed in the adult stage with strong expression in hypodermal cells and weaker expression in gut cells. Our findings suggest that spatial and temporal regulation of the cpr-1 gene is complex and involves activation by a GATA-like transcription factor.

Animals↗
PubMed1997

Deletion of a HoxD enhancer induces transcriptional heterochrony leading to transposition of the sacrum.

A phylogenetically conserved transcriptional enhancer necessary for the activation of Hoxd-11 was deleted from the HoxD complex of mice by targeted mutagenesis. While genetic and expression analyses demonstrated the role of this regulatory element in the activation of Hoxd-11 during early somitogenesis, the function of this gene in developing limbs and the urogenital system was not affected, suggesting that Hox transcriptional controls are different in different axial structures. In the trunk of mutant embryos, transcriptional activation of Hoxd-11 and Hoxd-10 was severely delayed, but subsequently resumed with appropriate spatial distributions. The resulting caudal transposition of the sacrum indicates that proper vertebral specification requires a precise temporal control of Hox gene expression, in addition to spatial regulation. A slight time delay in expression (transcriptional heterochrony) cannot be compensated for at a later developmental stage, eventually leading to morphological alterations.

Animals↗
PubMed2001

Regulation of gene expression by nitric oxide.

Nitric oxide (NO) modulates transcription factors that bind specific cis-regulatory DNA responsible for coordinating the spatial and temporal patterns of gene expression that are initiated by a changing microenvironment. In this way NO helps to orchestrate gene transcription and forms the basis of functional cell responses to accommodate metabolic requirements and to coordinate endogenous defense mechanisms against a variety of stress and disease conditions. There is marked overlap between the signalling pathways triggered by NO, superoxide, and hypoxia. Understanding the redox-based regulation of signal transduction and gene expression will provide insights into how cell activities are constantly coordinated and how promising new therapies may be developed.

Animals↗
PubMed1993

Type VII collagen gene expression in human umbilical tissue and cells.

BACKGROUND: Type VII collagen is a minor collagen found in anchoring fibrils. It is expressed predominantly by keratinocytes. In this study, we report the localization and spatial distribution of type VII collagen gene expression in the human umbilical cord, a fetal-derived tissue. EXPERIMENTAL DESIGN: Human umbilical cords were examined in indirect immunofluorescence studies, employing a mouse monoclonal anti-human type VII collagen antibody. Endothelial cells were cultured from the vein and grown on chamber slides for the detection of type VII collagen epitopes. In addition, cultured human umbilical vein cells were analyzed by Northern transfer analysis and by polymerase chain reaction for the expression of the corresponding gene. Fibroblast-like cells were isolated from the Wharton's jelly and were analyzed similarly for type VII collagen expression as well. RESULTS: We demonstrate that type VII collagen is expressed by human umbilical tissue and cells. Indirect immunofluorescence studies demonstrate the presence of type VII collagen epitopes in the epithelium surrounding a connective tissue region known as Wharton's jelly. In addition, there was low but detectable immunofluorescence signal associated with endothelial cells of blood vessels within the umbilical cord. In vitro, the fibroblast-like cells cultured from the Wharton's jelly showed prominent type VII collagen signal. This result was supported by the finding of high level of type VII collagen mRNA in these cells. The human endothelial cells from the vein demonstrated weak but detectable staining for type VII collagen, and the corresponding gene expression was shown by polymerase chain reaction analysis of the mRNA of the endothelial cells. CONCLUSIONS: The results show that umbilical tissue and cells, specifically those from the Wharton's jelly, are relatively enriched in type VII collagen. There is differential spatial localization of this collagen in the fetal tissue. The novel finding is that cells, other than epithelial cells such as keratinocytes, are able to express the type VII collagen gene.

Antibodies, Monoclonal↗
PubMed2026

A Practical Workflow for Spatial Transcriptomics Data Analysis: From Data Acquisition to Advanced Analyses.

Spatial transcriptomics (ST) profiles genome-wide gene expression while preserving the two-dimensional spatial context of mRNA molecules within tissue sections, enabling studies of tissue architecture and microenvironment-associated biology. However, ST analysis remains challenging because data import, quality control, integration, deconvolution, spatial statistics, and visualization often require multiple software environments and reproducible parameter choices. This protocol presents a practical computational workflow for public ST datasets in R, beginning with data acquisition and software setup and proceeding through Seurat-based data loading, quality control, normalization, multi-sample integration, clustering, and spatially variable gene analysis. The workflow then applies complementary deconvolution strategies, including reference-guided SPOTlight analysis and unsupervised STdeconvolve topic modeling, followed by Giotto-based spatial cell-cell communication analysis and interactive region-of-interest (ROI) selection using a custom Python Dash application. By emphasizing script-based execution, explicit parameter rationales, expected outputs, and troubleshooting checkpoints, the protocol provides an adaptable framework for standard array-based ST datasets and related platforms after dataset- and platform-specific parameter evaluation.

Spatial Transcriptomics↗
PubMed1998

Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis.

LMO4 is a novel member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors. LMO1, LMO2, and LMO4 have distinct expression patterns in adult tissue, and we demonstrate that nuclear retention of LMO proteins is enhanced by the nuclear LIM interactor (NLI). In situ hybridization to early mouse embryos of 8-14.5 days revealed a complex pattern of LMO4 expression spatially overlapping with NLI and LHX genes. LMO4 expression in somite is repressed in mice mutant for the segment polarity gene Mesp2 and expanded in Splotch mutants. During jaw and limb outgrowth, LMO4 and LMO2 expression define mesenchyme that is uncommitted to regional fates. Although both LMO2 and LMO4 are activated in thymic blast cells, only LMO4 is expressed in mature T cells. Mesenchymal and thymic blast cell expression patterns of LMO4 and LMO2 are consistent with the suggestion that LMO genes inhibit differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2026

SpatialRNA: a Python package for easy application of Graph Neural Network models on single-molecule spatial transcriptomics dataset.

SUMMARY: Image-based spatial transcriptomics (iST) deliver gene expression measurements of RNA transcripts in tissue slices with single-molecule resolution and spatial context preserved. Modern Graph Neural Network (GNN) models are promising methods for capturing the complex molecular and cellular phenotypes in tissues at single-transcript and single-cell levels. A key application of GNNs is the detection of spatial domains or niches, that is, groups of molecules and/or cells that collaboratively work together to produce complex phenotypes. Due to the vast number of detected transcripts in (iST) dataset, applying GNNs on RNA molecule graphs is not trivial. We present a Python package, SpatialRNA, for easy (sub)graph generation from tissue samples and provide comprehensive tutorials for convenient and efficient application of Graph Neural Network models under the PyG framework. This highly scalable tool comprehensively segments tissue into spatial domains, aiding in biological interpretation of iST data and its underlying molecular microenvironments. AVAILABILITY AND IMPLEMENTATION: The SpatialRNA package is freely accessible from online repository https://github.com/ruqianl/spatialrna and can be installed via pip. Comprehensive tutorials, guidance on parameter selection, and complete workflows of case studies are available from the documentation website https://ruqianl.github.io/spatialrna_docs/, and uploaded on Zenodo with a DOI 10.5281/zenodo.17339575.

Neural Networks, Computer↗
PubMed2000

Characterization of desmosomal component expression during palatogenesis.

Adhesion of the opposing palatal shelves is a critical first step in the mechanism for palatal fusion. Formation of desmosomal junctions between the two medial edge epithelia provides a mechanism for palatal shelf adhesion. RT-PCR and immunohistochemistry were used to determine the pattern of expression of desmosomal components during palatogenesis. Desmosomal expression was specifically upregulated in the medial edge epithelia (MEE) at the early stages of palatal fusion as detected by both immunohistochemistry and electron microscopy. RT-PCR characterization of the desmosomal components detected all known elements, except desmocollin 1 (DSC1). Desmocollin 2 (DSC2) was expressed as both the DSC2a and DSC2b variants. The two variants are expressed at the same level. Western analysis of desmoglein expression paralleled the RT-PCR result. The temporal and spatial upregulation of desmosomal gene expression is evidence that the MEE induce new gene expression required to accomplish palatal shelf adhesion and initiate the first stage of palatal fusion.

Animals↗
PubMed1997

Expression of DA11, a neuronal-injury-induced fatty acid binding protein, coincides with axon growth and neuronal differentiation during central nervous system development.

DA11 is the first fatty acid binding protein (FABP) for which gene expression has been shown to be upregulated following neuronal injury in the adult peripheral nervous system. To understand better the potential regulatory role(s) of this unique FABP in axonal growth and neuronal differentiation, we undertook a temporal and spatial study of DA11 gene expression in the developing rat central nervous system (CNS). Transient upregulation of DA11 mRNA and protein levels in CNS tissues were quantified by Northern blot hybridization and Western immunoblot analyses at different developmental ages. Homogenates of embryonic and neonatal cerebral cortex, cerebellum, brain stem, and hippocampal tissues contained 100-fold more DA11 mRNA and protein than corresponding adult tissues. Significant increase in DA11 mRNA was observed as early as embryonic day (E) 14 in cerebral cortex and cerebellum and E19 in brain stem and hippocampus. Postnatal levels of DA11 remained elevated through postnatal day (P) 10 in cerebral cortex, P14 in brain stem and hippocampus, and P20 in cerebellum. Localization of DA11-like immunoreactivity to specific CNS tissues, cell types, and intracellular compartments at P9 revealed a spatial pattern of neuronal expression different than that reported for other FABPs. DA11 protein was detected in the nucleus, cytoplasm, axons, and dendrites of differentiating neurons in cerebral cortex, hippocampus, cerebellum, brain stem, spinal cord, and olfactory bulb. The strong association of DA11 gene expression with development throughout the CNS suggests that this unique FABP plays an important role in axonal growth and neuronal differentiation in many different neuronal populations.

Animals↗
PubMed2006

Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling.

Spatially and temporally coordinated changes in gene expression are crucial to orderly progression of embryogenesis. We combine mouse genetics with experimental manipulation of signalling to analyze the kinetics by which the SHH morphogen and the BMP antagonist gremlin 1 (GREM1) control gene expression in the digit-forming mesenchyme of mouse limb buds. Although most mesenchymal cells respond rapidly to SHH signalling, the transcriptional upregulation of specific SHH target signals in the mesenchyme occurs with differential temporal kinetics and in a spatially restricted fashion. In particular, the expression of the BMP antagonist Grem1 is always upregulated in mesenchymal cells located distal to the SHH source and acts upstream of FGF signalling by the apical ectodermal ridge. GREM1/FGF-mediated feedback signalling is, in turn, required to propagate SHH and establish the presumptive digit expression domains of the Notch ligand jagged 1 (Jag1) and 5'Hoxd genes in the distal limb bud mesenchyme. Their establishment is significantly delayed in Grem1-deficient limb buds and cannot be rescued by specific restoration of SHH signalling in mutant limb buds. This shows that GREM1/FGF feedback signalling is required for regulation of the temporal kinetics of the mesenchymal response to SHH signalling. Finally, inhibition of SHH signal transduction at distinct time points reveals the differential temporal dependence of Grem1, Jag1 and 5'Hoxd gene expression on SHH signalling. In particular, the expression of Hoxd13 depends on SHH signal transduction significantly longer than does Hoxd11 expression, revealing that the reverse co-linear establishment, but not maintenance of their presumptive digit expression domains, depends on SHH signalling.

Animals↗
PubMed2005

Synthetic biology: engineering Escherichia coli to see light.

We have designed a bacterial system that is switched between different states by red light. The system consists of a synthetic sensor kinase that allows a lawn of bacteria to function as a biological film, such that the projection of a pattern of light on to the bacteria produces a high-definition (about 100 megapixels per square inch), two-dimensional chemical image. This spatial control of bacterial gene expression could be used to 'print' complex biological materials, for example, and to investigate signalling pathways through precise spatial and temporal control of their phosphorylation steps.

Agar↗
PubMed1991

Tissue-specific and developmental regulation of rod opsin chimeric genes in transgenic mice.

Chimeric gene fusions between 4.4 kb of rod opsin 5' flanking sequence fused to a diphtheria toxin gene and 4.4 kb or 500 bp of rod opsin 5' flanking sequence fused to the E. coli IacZ gene were used to generate transgenic mice for analysis of cell type-specific expression and temporal and spatial distribution of reporter gene product during retinal development. Opsin-diphtheria toxin transgene expression evoked photoreceptor-specific cell death. The 4.4 kb opsin-IacZ transgene followed temporal and spatial gradients of expression that approximate opsin expression. The 500 bp opsin fragment targeted expression to photoreceptors, but expression was weaker and nonuniform, suggesting that elements located upstream may be required for enhanced and uniform spatial expression.

Animals↗
PubMed1999

Small subfamily of olfactory receptor genes: structural features, expression pattern and genomic organization.

Olfactory receptors of the OR37 subfamily are characterized by distinct sequence features and are expressed in neurons segregated in a restricted area of the olfactory epithelium. In the present study, we have characterized the complement of OR37-like genes in the mouse. Five OR37-like genes were identified. They reside within only 60kb of DNA on chromosome 4. About 70kb distant from this cluster, two additional olfactory receptor genes are located, which are members of distinct receptor subfamilies. Phylogenetic analysis demonstrated that the two physically linked receptors are closely related to the OR37 subfamily. Studies of gene expression showed that both genes are also expressed in clustered neuron populations located in the typical OR37 region of the epithelium. These data suggest the involvement of locus-dependent mechanisms for the spatial control of OR gene expression.

Amino Acids↗