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Results for “spatial gene expression”

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PubMed1998

Unilateral hippocampal lesions in newborn and adult rats: effects on spatial memory and BDNF gene expression.

Subcortical damage at birth often produces more severe deficits than similar lesions in an adult. In the present study, effects of unilateral electrolytic hippocampal ablations made on postnatal day 1 or in 3-month-old adult rats, were compared. Exploratory behavior and spatial navigation in the Morris water maze (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal damage did not respond to novelty in the environment and did not learn to find the hidden platform in the MWM. Rats lesioned as adults did learn the water maze task, but slower than controls. We hypothesized that behavioral deficits observed in rats lesioned at birth, may be due, in part, to neurochemical dysfunction of the contralateral hippocampus. Specifically, cholinergic and GABAergic neurotransmission were assessed by measuring choline-acetyltransferase (ChAT) and GABAdecarboxylase (GAD) activity. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the remaining (contralateral) hippocampus. Of these molecules, only BDNF gene expression was significantly reduced (by 30%) at 8 and 20 weeks after neonatal and adult unilateral ablation. The similar reduction in BDNF mRNA in both treatment groups does not correspond with the lesion's differential effect on memory function. However, the more severe learning impairment after neonatal lesion may reflect increased dependence on trophins during development.

Aging↗
PubMed2004

The murine Cyp1a1 gene is expressed in a restricted spatial and temporal pattern during embryonic development.

In adult mice the cytochrome P450 Cyp1a1 gene is not constitutively expressed but is highly inducible by foreign compounds acting through the aryl hydrocarbon (Ah) receptor. However, the expression profile of the Cyp1a1 gene in the developing embryo is not well under-stood. Using established transgenic mouse lines where 8.5 kb of the rat CYP1A1 promoter is cloned upstream of the lacZ reporter gene (1), we describe the expression of the CYP1A1-driven reporter gene in all tissues through-out stages E7-E14 of embryonic development. In contrast to the absence of constitutive Cyp1a1 and lacZ transgene expression in tissues of the adult mouse, a constitutive cell-specific and time-dependent pattern of CYP1A1 promoter activity was observed in the embryo. This expression pattern was confirmed as reflecting the endogenous gene by measuring Cyp1a1 mRNA levels and protein expression by immunohistochemistry. The number of cells displaying endogenous CYP1A1 activity could be increased in the embryo upon xenobiotic challenge, but only within areas where the CYP1A1 promotor was already active. When reporter mice were bred onto a genetic background expressing a lower affinity form of the Ah receptor (DBA allele), transgene and murine Cyp1a1 protein expression were both attenuated in the adult mouse liver upon xenobiotic challenge. By comparison, constitutive CYP1A1 promoter activity in the embryo was identical in the presence of either the high or low affinity Ah receptor. These novel data suggest that the Cyp1a1 protein may play a role in murine development and that regulation of the Cyp1a1 gene during this period is either through the action of a high affinity Ah receptor ligand or by an alternative regulatory pathway.

Animals↗
PubMed2001

Differential gene expression governed by chromosomal spatial asymmetry.

The activity of the transcription factor sigmaF is confined to one (the forespore) of two cells created by asymmetric division during sporulation in B. subtilis. We show that sigmaF activation is partly governed by the position of the gene for the unstable anti-sigmaF factor SpoIIAB. Because cytokinesis precedes chromosome segregation, most of the chromosome is translocated into the forespore after division. We hypothesize that because spoIIAB enters the forespore late, SpoIIAB lost to proteolysis is temporarily not replenished. Thus, chromosome asymmetry would be translated into the asymmetric distribution of SpoIIAB. Supporting this idea, transposition of spoIIAB to sites present in the forespore at the time of division impaired sporulation when a second pathway that participates in sigmaF activation was disabled.

Bacillus subtilis↗
PubMed2004

Computational discovery of DNA motifs associated with cell type-specific gene expression in Ciona.

Temporally and spatially co-expressed genes are expected to be regulated by common transcription factors and therefore to share cis-regulatory elements. In the ascidian Ciona intestinalis, the whole-genome sequences and genome-scale gene expression profiles allow the use of computational techniques to investigate cis-elements that control transcription. We collected 5' flanking sequences of 50 tissue-specific genes from genome databases of C. intestinalis and a closely related species Ciona savignyi. We searched for DNA motifs over-represented in upstream regions of a group of co-expressed genes. Several motifs were distributed predominantly in upstream regions of photoreceptor, pan-neuronal, or muscle-specific gene groups. One muscle-specific motif, M2, was distributed preferentially in regions from -200 to -100 bp relative to the translational start sites. Promoters of muscle-specific genes of C. intestinalis were isolated, connected with a green fluorescent protein gene (GFP), and introduced into C. intestinalis embryos. In muscle cells, these promoters specifically drove GFP expression, which mutations of the M2 sites greatly reduced. When M2 sites were located upstream of a basal promoter, the reporter GFP was specifically expressed in muscle cells. These results suggest the validity of our computational prediction of cis-regulatory elements. Thus, bioinformatics can help identify cis-regulatory elements involved in chordate development.

Animals↗
PubMed1994

Novel vascular cell-specific genes whose expression is regulated temporally and spatially during vascular system development.

We have isolated three cDNA clones (TED2, TED3, and TED4) for genes expressed preferentially in cells that redifferentiate into tracheary elements from mesophyll cells isolated from leaves of Zinnia elegans. Sequence analyses of TED clones revealed that TED2 encodes a hydrophobic polypeptide with a significant similarity to the guinea pig lens-specific protein (zeta-crystallin) and that the deduced polypeptide of TED3 may be a novel cell wall protein. In situ hybridization of the TED probes with young Zinnia seedlings showed that expression of the three TED genes was restricted to vascular cells and regulated in a temporal and spatial manner during vascular development. TED3 transcripts were localized specifically to a few cells that are to differentiate or are differentiating into tracheary elements in all organs examined. TED4 transcripts were present mainly in the immature primary xylem both of cotyledons and of the boundary region between the root and hypocotyl and in the procambium of roots. In contrast, TED2 transcripts accumulated not only in immature primary xylem cells but also in immature phloem cells both in roots and in the boundary region between the root and hypocotyl. In addition, TED2 transcripts were expressed in the procambium cells of roots. In cotyledons, TED2 transcripts did not accumulate in xylem or phloem cells but only in two regions that might form a new vein just outside the phloem of the main leaf vein. Taken together, our findings indicate that TED2, TED3, and TED4 can be novel and efficient markers for development of the vascular system.

Amino Acid Sequence↗
PubMed2004

Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene.

BACKGROUND: The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial) gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis. RESULTS: The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-alpha and -gamma) and two other long isoforms (Spatial-delta and -epsilon) comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-beta, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-beta protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved. CONCLUSIONS: The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-alpha, -beta and -gamma) highly expressed in the thymus and two long isoforms (Spatial-delta and -epsilon) highly expressed in the testis. These alternative spliced variants could have a tissue specific function.

Alternative Splicing↗
PubMed1989

Altered expression of spatially regulated embryonic genes in the progeny of separated sea urchin blastomeres.

We have examined the importance of the extracellular environment on the ability of separated cells of sea urchin embryos (Strongylocentrotus purpuratus) to carry out patterns of mRNA accumulation and decay characteristic of intact embryos. Embryos were dissociated into individual blastomeres at 16-cell stage and maintained in calcium-free sea water so that daughter cells continuously separated. Levels of eleven different mRNAs in these cells were compared to those in control embryos when the latter reached mesenchyme blastula stage, by which time cells in major regions of the intact embryo have assumed distinctive patterns of message accumulation. Abrogation of interactions among cells resulted in marked differences in accumulation and/or turnover of the individual mRNAs, which are expressed with diverse temporal and spatial patterns of prevalence in intact embryos. In general, separated cells are competent to execute initial events of mRNA accumulation and decay that occur uniformly in most or all blastomeres of the intact embryo and are likely to be regulated by maternal molecules. The ability of separated cells to accumulate mRNAs that appear slightly later in development depends upon the presumptive tissue in which a given mRNA is found in the normal embryo. Messages that normally accumulate in cells at the vegetal pole also accumulate in dissociated cells either at nearly normal levels or at increased levels. In one such case, that of actin CyIIa, which is normally restricted to mesenchyme cells, in situ hybridization demonstrates that the fraction of dissociated cells expressing this message is 4- to 5-fold higher than in the normal embryo. In contrast, separated cells accumulate significant levels of a message expressed uniformly in the early ectoderm but are unable to execute accumulation and decay of different messages that distinguish oral and aboral ectodermal regions. These data are consistent with the idea that interactions among cells in the intact embryo are important for both positive and negative control of expression of different genes that are early indicators of the specification of cell fate.

Animals↗
PubMed1992

Spatial restriction of AChR gene expression to subsynaptic nuclei.

Acetylcholine receptors (AChRs) and the mRNAs encoding the four AChR subunits are highly concentrated in the synaptic region of skeletal myofibers. The initial localization of AChRs to synaptic sites is triggered by the nerve and is caused, in part, by post-translational mechanisms that involve a redistribution of AChR protein in the myotube membrane. We have used transgenic mice that harbor a gene fusion between the murine AChR delta subunit gene and the human growth hormone gene to show that innervation also activates two independent transcriptional pathways that are important for establishing and maintaining this non-uniform distribution of AChR mRNA and protein. One pathway is triggered by signal(s) that are associated with myofiber depolarization, and these signals act to repress delta subunit gene expression in nuclei throughout the myofiber. Denervation of muscle removes this repression and causes activation of delta subunit gene expression in nuclei in non-synaptic regions of the myofiber. A second pathway is triggered by an unknown signal that is associated with the synaptic site, and this signal acts locally to activate delta subunit gene expression only in nuclei within the synaptic region. Synapse-specific expression, however, does not depend upon the continuous presence of the nerve, since transcriptional activation of the delta subunit gene in subsynaptic nuclei persists after denervation. Thus, the nuclei in the synaptic region of multinucleated skeletal myofibers are transcriptionally distinct from nuclei elsewhere in the myofiber, and this spatially restricted transcription pattern is presumably imposed initially by the nerve.

Animals↗
PubMed2006

A proposed metric for assessing the measurement quality of individual microarrays.

BACKGROUND: High-density microarray technology is increasingly applied to study gene expression levels on a large scale. Microarray experiments rely on several critical steps that may introduce error and uncertainty in analyses. These steps include mRNA sample extraction, amplification and labeling, hybridization, and scanning. In some cases this may be manifested as systematic spatial variation on the surface of microarray in which expression measurements within an individual array may vary as a function of geographic position on the array surface. RESULTS: We hypothesized that an index of the degree of spatiality of gene expression measurements associated with their physical geographic locations on an array could indicate the summary of the physical reliability of the microarray. We introduced a novel way to formulate this index using a statistical analysis tool. Our approach regressed gene expression intensity measurements on a polynomial response surface of the microarray's Cartesian coordinates. We demonstrated this method using a fixed model and presented results from real and simulated datasets. CONCLUSION: We demonstrated the potential of such a quantitative metric for assessing the reliability of individual arrays. Moreover, we showed that this procedure can be incorporated into laboratory practice as a means to set quality control specifications and as a tool to determine whether an array has sufficient quality to be retained in terms of spatial correlation of gene expression measurements.

Algorithms↗
PubMed2005

Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone.

Extracellular matrix (ECM) mineralization is a physiological process in bone and a pathological one in soft tissues. The mechanisms determining the spatial restriction of ECM mineralization to bone physiologically are poorly understood. Here we show that a normal extracellular phosphate concentration is required for bone mineralization, while lowering this concentration prevents mineralization of any ECM. However, simply raising extracellular phosphate concentration is not sufficient to induce pathological mineralization, this is because of the presence in all ECMs of pyrophosphate, an inhibitor of mineralization. ECM mineralization occurs only in bone because of the exclusive coexpression in osteoblasts of Type I collagen and Tnap, an enzyme that cleaves pyrophosphate. This dual requirement explains why Tnap ectopic expression in cells producing fibrillar collagen is sufficient to induce pathological mineralization. This study reveals that coexpression in osteoblasts of otherwise broadly expressed genes is necessary and sufficient to induce bone mineralization and provides evidence that pathological mineralization can be prevented by modulating extracellular phosphate concentration.

Alkaline Phosphatase↗
PubMed2002

Spatial and temporal variation of passer Per2 gene expression in two distinct cell groups of the suprachiasmatic hypothalamus in the house sparrow (Passer domesticus).

In mammals, the major pacemaker controlling circadian rhythmicity is located in the hypothalamic suprachiasmatic nuclei. Although there is evidence for the presence of a hypothalamic circadian oscillator in birds from lesioning studies, neuroanatomical, neurochemical and functional investigations have failed to identify its exact location. Two cell groups in the avian hypothalamus have been shown to bear characteristics of the mammalian suprachiasmatic nucleus: the suprachiasmatic nucleus and the lateral hypothalamic retinorecipient nucleus. We cloned an avian period homologue (pPer2) and investigated the temporal and spatial expression pattern of this gene in the house sparrow hypothalamus using in situ hybridization. Applying quantitative morphometry, we found rhythmic expression of pPer2 during light-dark as well as in constant conditions in the suprachiasmatic nucleus and in the lateral hypothalamus. The temporal and spatial distribution of pPer2 expression in the suprachiasmatic nucleus suggest a longitudinal compartmentalization of the nucleus with period gene expression being initiated in the most rostral portion of the suprachiasmatic nucleus before lights on. In the lateral hypothalamus, phasing of pPer2-rhythmicity appeared different from the suprachiasmatic nucleus. The major difference between light-dark and constant conditions was a decrease in the amplitude of pPer2 rhythmicity in the suprachiasmatic nucleus. Our data demonstrate that, unlike in mammals, Per gene expression in the suprachiasmatic hypothalamus of the house sparrow is not confined to a single cell group, indicating a more complex organization of the circadian oscillator in the hypothalamus of birds.

Animals↗
PubMed2000

cDNA subtraction cloning reveals novel genes whose temporal and spatial expression indicates association with trophoblast invasion.

Trophoblast invasion is a critical process in development of most mammals that shares similarities with the invasive behavior of tumor cells. In the present investigation, a cDNA subtraction library was constructed between invasive trophoblast at day 8 of murine development and mature noninvasive placenta at day 18 of gestation. One of the differentially expressed clones, Epcs26, was mapped to the X chromosome and revealed no homology to any known gene. It was predominantly expressed in parietal endoderm, undifferentiated cells of the ectoplacental cone, and a few trophoblast giant cells. Another gene, designated Epcs50, was mapped to chromosome 19. It exhibited homologies to the mouse Mps1 gene and, like Mps1, may have a distant relationship to the lytic protein perforin. High expression was detected in parietal endoderm cells and in a subset of secondary trophoblast giant cells. Two sequences, Epcs24 and Epcs68, exhibited an extensive open reading frame that shared the common features of the cysteine proteinase cathepsin L. Expression was confined to an undefined subpopulation of trophoblast giant cells. Both genes were mapped to chromosome 13 in close proximity to cathepsins L and J. The known functions of MPS1 and cathepsin L proteins indicate that the related proteins EPCS50, EPCS24, and EPCS68 participate in conferring invasive properties to the mouse trophoblast.

Amino Acid Sequence↗
PubMed2002

Identification of genes that are associated with DNA repeats in prokaryotes.

Using in silico analysis we studied a novel family of repetitive DNA sequences that is present among both domains of the prokaryotes (Archaea and Bacteria), but absent from eukaryotes or viruses. This family is characterized by direct repeats, varying in size from 21 to 37 bp, interspaced by similarly sized non-repetitive sequences. To appreciate their characteri-stic structure, we will refer to this family as the clustered regularly interspaced short palindromic repeats (CRISPR). In most species with two or more CRISPR loci, these loci were flanked on one side by a common leader sequence of 300-500 b. The direct repeats and the leader sequences were conserved within a species, but dissimilar between species. The presence of multiple chromosomal CRISPR loci suggests that CRISPRs are mobile elements. Four CRISPR-associated (cas) genes were identified in CRISPR-containing prokaryotes that were absent from CRISPR-negative prokaryotes. The cas genes were invariably located adjacent to a CRISPR locus, indicating that the cas genes and CRISPR loci have a functional relationship. The cas3 gene showed motifs characteristic for helicases of the superfamily 2, and the cas4 gene showed motifs of the RecB family of exonucleases, suggesting that these genes are involved in DNA metabolism or gene expression. The spatial coherence of CRISPR and cas genes may stimulate new research on the genesis and biological role of these repeats and genes.

Amino Acid Sequence↗
PubMed1997

Control of cell-type specific gene expression in Dictyostelium by the general transcription factor GBF.

To understand how positional information within an organism specifies patterning during development, we are analyzing spatially regulated gene expression in Dictyostelium. CAR3 is a member of the cAMP, 7-span receptor family which directs the transition from unicellular to multicellular organism and regulates cellular differentiation and pattern formation. CAR3 mRNA is expressed maximally at 8-10 hours of development, as individual cells aggregate and differentiate, and is accumulated to equivalent levels in all cells. CAR3 is also induced in shaking cultures by response to extracellular cAMP. We now show, by extensive mutagenesis, that the maximum length of contiguous sequences required for accurate spatiotemporal regulation of CAR3 is approx. 350 bp. These sequences include three significant elements located in upstream and transcribed regions. Arrays of G-boxes (GBF regulatory sites) are centered near positions -165 and +50 and, although either is sufficient for induction by cAMP and expression in prespore cells, both are required for expression in prestalk cells. Another GC-rich element near position -80 is required for maximal expression of prespore-specific constructs, although full-length promoters carrying clustered mutations through the -80 region are still expressed in all cells, but with slightly reduced expression. Spatiotemporal expression of CAR3 during development, thus, requires cell-specific combinatorial interactions of multiple but redundant regulatory components. These essential elements are located in upstream and transcribed regions. However, most surprisingly, a primary control for spatial patterning of CAR3 expression appears to be mediated by GBF, a general transcription factor expressed ubiquitously during Dictyostelium development following early aggregation.

Animals↗
PubMed1988

The expression of beta 1 and beta 3 tubulin genes of Drosophila melanogaster is spatially regulated during embryogenesis.

In Drosophila beta tubulins are encoded by a small gene family and the four members of this family are differentially expressed. mRNAs transcribed from two of these genes, namely the beta 1 and beta 3 tubulin genes, are abundant during embryogenesis. While the beta 1 tubulin gene is constitutively expressed during development, beta 3 mRNA is restricted to two distinct phases: mid embryogenesis and metamorphosis. The transcription initiation sites are identical in both these stages and comparison of presumptive promoter regions reveals no extensive homologies between the genes. In situ localization shows beta 1 tubulin mRNA to be maternally expressed in the nurse cells of the egg chambers and evenly distributed during early embryogenesis. In contrast, during later stages of embryogenesis beta 1 tubulin transcripts are predominantly expressed in neural derivatives. The beta 3 tubulin gene expression is also spatially regulated, beta 3 mRNA being restricted to the mesoderm.

Animals↗
PubMed1993

Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-beta 1 revealed by in situ hybridization during experimentally induced liver fibrosis in the rat.

Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta 1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined. Using in situ hybridization combined with immunocytochemical staining for cell-type characteristic markers, we demonstrate spatial and temporal expression patterns specific for each of the genes. Biglycan gene expression levels coincided tightly with the activity and extent of fibrosis, fat-storing cells and their transformed form, the myofibroblast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory stage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected solely in periportal fields with enhanced bile duct proliferation. Transforming growth factor-beta 1 expression was undetectable in normal liver. During the subacute inflammatory stage, a hepatocyte subpopulation expressing low levels of transforming growth factor-beta 1 occurred at the limiting plate. With the progression of fibrosis, transforming growth factor-beta 1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa.

Animals↗
PubMed1996

Separate cis-acting elements determine the expression of mouse Dbx gene in multiple spatial domains of the central nervous system.

Dbx, a divergent homeobox gene, is expressed in a regionally restricted pattern in the developing mouse central nervous system (CNS). In order to understand its spatial regulation, we have isolated a cis-regulatory region using a reporter gene analytical approach in transgenic mice. A 5.7 kb DNA fragment that contains the transcriptional start site of the Dbx gene is sufficient to direct the expression of the transgene to various domains of the CNS in a temporally regulated fashion. The transgene expression can be detected between 9.5 and 15.5 days post coitum in embryos in the fore-, mid- and hindbrain and spinal cord in regions where the endogenous gene is expressed. Additionally, transgene expression can also be detected in the oculomotor nerve (cranial nerve III). The expression of the transgene closely resembles that of the Dbx gene with minor, but interesting differences. These results suggest that major cis-acting elements reside within a 5.7 kb DNA fragment located 5' of the Dbx gene. Further deletion analysis shows that at least two independently regulated elements are present within this DNA fragment: an element that directs expression to the brain and spinal cord and a second element that directs expression to the oculomotor nerve.

Amino Acid Sequence↗
PubMed1988

Molecular structure and spatial expression of a homeobox gene from the labial region of the Antennapedia-complex.

We report the molecular characterization of a homeobox-containing gene that maps at 84A in the proximal region of the Antennapedia-complex. The structure and complete sequence are presented. Deletion analysis indicates that the cloned gene, F24, most likely corresponds to the labial (lab) gene. Northern blot experiments show a single approximately 3-kb transcript that is expressed at all embryonic stages from cellular blastoderm onwards and during larval development. The homeobox is split by an intron in the region which encodes the putative DNA-binding helix, a splicing position for homeobox-containing genes which is unique so far. The 5' part of the gene contains four M-repeat sequences (CAA/G repeats) in the protein-coding region. In situ hybridization to the transcripts during embryogenesis reveals two domains of expression. The anterior one is located in parts of the developing head, mainly in the hypopharyngeal organ and in anterior parts of the mandibular lobe, and is restricted to the ectoderm. The posterior domain is part of the posterior midgut primordium (endoderm), that invaginates and later contacts the endoderm cells from the anterior midgut invagination.

Amino Acid Sequence↗