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At least 343 records · Page 19Linked to original sources
PubMed1997

Structure and spatial expression of the Manduca sexta MSCP14.6 cuticle gene.

The genomic and cDNA sequences of the MSCP14.6 gene section, which encodes a Manduca sexta cuticle protein, have been determined. The genomic sequence presented here includes 1428 N of 5' flanking DNA, 1587 N of transcribed DNA, and 465 N of 3' flanking DNA. The intron/exon boundaries mapped by comparison of these sequences were confirmed by primer extension and SI nuclease mapping. Prior work showed that the RNA produced by this gene is regulated both temporally and spatially during larval, pupal, and adult development, and also showed that both 20-hydroxyecdysone (20E) and juvenile hormone (JH) are important in controlling the amount of RNA present in the epidermis (Riddiford et al., 1986). In situ hybridizations show that MSCP14.6 is expressed throughout the epidermis in larvae and is spatially restricted in pharate pupal and pharate adult stages. The results presented here delimiting the transcription unit and 5' flanking DNA of the MSCP14.6 gene will facilitate further research to determine the DNA elements necessary for regulation of gene expression.

Amino Acid Sequence↗
PubMed1990

Expression of GHF-1 protein in mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity.

The relationship between expression of the pituitary-specific transcription factor, GHF-1, and activation of the growth hormone and prolactin genes during mouse anterior pituitary development was investigated. While GHF-1 transcripts were detected within 24 hr of the first observable events in anterior pituitary differentiation, no GHF-1 protein could be detected until about 3 days later. The appearance of GHF-1 protein showed good temporal and spatial correlation with activation of the growth hormone gene. Prolactin gene expression, on the other hand, was observed transiently during embryonic day 16 in two different populations of cells, of which the major one does not contain GHF-1 or growth hormone. These results suggest that expression of GHF-1 is controlled both transcriptionally and posttranscriptionally. The spatial and temporal correlation between the appearance of GHF-1 protein and growth hormone gene activation suggests that GHF-1 is responsible for this very last step in the specialization of somatotrophic cells.

Animals↗
PubMed2001

Possible roles for stanniocalcin during early skeletal patterning and joint formation in the mouse.

Stanniocalcin (STC) is a polypeptide hormone discovered first in fish and more recently in mammals. In mammals, the gene is widely expressed and the hormone is, so far, known to be involved in regulating the transport of calcium or phosphate across renal and gut epithelia, and into neuronal cells. Gene expression is also high during development, and in an earlier study we mapped the temporal and spatial pattern of gene expression in the mouse urogenital system. Our data suggested that STC probably acted as a signaling molecule that was produced in mesenchyme cells and targeted to epithelial cell layers in both kidney and testes. Here we have examined STC mRNA and protein distributions between developmental stages E10.5 and E18.5 in the axial and appendicular skeleton. In the axial skeleton, STC was transiently expressed in a rostral-caudal fashion during vertebral development; protein appeared to be made in intervertebral disc mesenchyme cells and targeted to vertebral hypertrophic and prehypertrophic chondrocytes. By stage E18.5, the STC gene was active only in vertebral perichondrocytes. The pattern of expression in the appendicular skeleton was equally striking. Early in development, STC gene expression defined the initial lengths of bone primordia. The gene was expressed in mesenchyme cells at either ends of precartilaginous condensations defining future long bones and the secreted protein was targeted to the chondroblasts. Later on during joint formation, STC was highly expressed in interzone cells that defined all future joints. After cavitation, STC gene expression was greatest in perichondrocytes lining the joints. Underlying resting, proliferative and prehypertrophic chondrocytes appeared to be the targets of STC both during and after cavitation. Therefore, its pattern of expression was indicative of a role in early skeletal patterning and joint formation. Moreover, as occurs during urogenital development, it appeared that STC is made in undifferentiated mesenchyme cells and sequestered by those destined to differentiate.

Animals↗
PubMed2006

MicroRNAs in mammalian development.

Development in mammals is a complex process requiring gene expression to be spatially and temporally well-regulated. Factors modulate gene functioning by controlling transcription, translation, or mRNA degradation. microRNAs (miRNAs) are a group of small RNA molecules (approximately 22 nucleotides) that attenuate gene activity posttranscriptionally by suppressing translation or destabilizing mRNAs. miRNAs have been recently validated to regulate many animal developmental events including proliferation, differentiation, and apoptosis. Many miRNAs display intriguing expression and functioning patterns throughout these pathways. Here we will review achievements to date about studies of how miRNAs affect a variety of animal developmental transitions, from the formation of early embryos to the generation of highly specialized tissues.

Animals↗
PubMed2025

BISON: bi-clustering of spatial omics data with feature selection.

MOTIVATION: The advent of next-generation sequencing-based spatially resolved transcriptomics (SRT) techniques has reshaped genomic studies by enabling high-throughput gene expression profiling while preserving spatial and morphological context. Understanding gene functions and interactions in different spatial domains is crucial, as it can enhance our comprehension of biological mechanisms, such as cancer-immune interactions and cell differentiation in various regions. It is necessary to cluster tissue regions into distinct spatial domains and identify discriminating genes (DGs) that elucidate the clustering result, referred to as spatial domain-specific DGs. Existing methods for identifying these genes typically rely on a two-stage approach, which can lead to the phenomenon known as double-dipping. RESULTS: To address the challenge, we propose a unified Bayesian latent block model that simultaneously detects a list of DGs contributing to spatial domain identification while clustering these DGs and spatial locations. The efficacy of our proposed method is validated through a series of simulation experiments, and its capability to identify DGs is demonstrated through applications to benchmark SRT datasets. AVAILABILITY AND IMPLEMENTATION: The R/C++ implementation of BISON is available at https://github.com/new-zbc/BISON.

Software↗
PubMed2001

Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice.

Cre-loxP based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. We reported earlier the generation of transgenic mice that express the Cre recombinase under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). These mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. We have now characterized in depth the expression of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporter strain to determine the temporal and spatial activation of Cre on the level of single cells. Our results show that MMTV-mediated Cre-activation is restricted to specific cell types of various secretory tissues and the hematopoietic system. Secondly, the timing of Cre expression varies between tissues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggesting a strong influence of steroid hormones on the transcriptional activation of the MMTV-LTR. Thirdly, Cre expression in the female germline is restricted to individual mouse lines and is therefore dependent on the site of integration of the transgene. Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes.

Animals↗
PubMed1997

Gene expression of type II collagens in chondro-osteophytes in experimental osteoarthritis.

The formation of chondro-osteophytes in osteoarthritic joints is a unique example of adult neochondrogenesis that bears some similarities to growth plate elongation and fracture callus formation. This study uses in situ hybridization histochemistry to define the molecular phenotype of cells in active chondro-osteophytes. Chondro-osteophytes are composed of fibrocytes and osteoblasts that express type I procollagen mRNA, mesenchymal prechondrochytes that express type IIA procollagen mRNA, and maturing chondrocytes that express type IIB procollagen mRNA. Based on the spatial pattern of gene expression and cytomorphology, the neochondrogenesis associated with chondro-osteophyte formation closely resembles that of healing fracture callus.

Animals↗
PubMed1997

Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma.

Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.

Apoptosis↗
PubMed1995

Temporal and spatial expression of an adult cuticle protein gene from Drosophila suggests that its protein product may impart some specialized cuticle function.

An adult cuticle protein gene (Dacp-1) from Drosophila melanogaster has been isolated and characterized. This gene was classified as an adult cuticle protein gene because it maintains the conserved structure of other cuticle protein genes, the sequence of its conceptual translation product contains a repeated motif that is found almost exclusively in a subset of adult cuticle proteins from Locust migratoria, and the gene is expressed in the epidermis underlying the head and thoracic cuticle. The bulk of Dacp-1 expression starts approximately 72 hr after pupariation, peaks approximately 12 hr after eclosion, and decreases thereafter to undetectable levels by 3 days after eclosion. The stage specificity and spatial restriction of Dacp-1 expression as well as the physical properties of its conceptual translation product suggest that it may be involved in some specialized function such as thickening of the adult cuticle.

Amino Acid Sequence↗
PubMed1995

Proliferation-associated differences in the spatial and temporal expression of gap junction genes in rat liver.

After a 70% partial hepatectomy (PH), the steady-state levels of Connexin (Cx)32, Cx26, and Cx43 messenger RNA (mRNA) transcripts each displayed unique patterns of temporal expression. Within 1 hour after surgical resection, increased expression of all three Cx mRNAs was observed. Subsequently, the level of Cx32 mRNA transcripts transiently decreased to a nadir at 12 hours. Comparisons of the spatial changes with previously reported hepatocyte proliferation kinetics induced by PH demonstrated that hepatocytes before S-phase "remodel" their GJs. Within 1 to 5 hours post-PH, midzonal hepatocytes exhibited diffuse membrane staining different from the normal punctate distribution. Subsequently, midzonal hepatocytes expressed colocalized punctate Cx32 and Cx26 immunostaining. Because the changes occurred in midzonal hepatocytes before 24 hours post-PH, near the peak of hepatocyte DNA synthesis, these findings indicate that Cx26 is enhanced in hepatocytes before the onset of S-phase. In contrast to the restricted expression of Cx43 in Glisson's capsule in adult liver, Cx43 protein and mRNA were enhanced specifically in proliferating bile duct and perisinusoidal cells post-PH. PH performed during continuous administration of 2-acetylaminofluorene (AAF) prevented changes in Cx32 and Cx26 staining observed in the absence of AAF. Proliferating oval cells were found to express diffuse Cx43 immunoreactivity. On day 11 post-PH and AAF, basophilic hepatocytes displayed both punctate Cx32 and Cx26 staining, whereas bile ducts and perisinusoidal cells expressed Cx43. These findings indicate that alterations in Cx32 and Cx26 expression occur rapidly in hepatocytes stimulated to proliferate and that several nonparenchymal liver cell types upregulate Cx43 expression when induced to proliferate. Differentiation of oval cells into basophilic hepatocytes resulted in their expression of Cx32 and Cx26.

Animals↗
PubMed1995

Copy-dependent and position-independent expression of rat aldolase A gene.

In order to understand the molecular mechanisms of the temporal and spatial differences of gene expression in higher organisms, rat aldolase A gene carrying two distinct promoters was introduced into fertilized eggs and the resulting transgenic mice were analyzed. The transgene expression is tissue-specific and is developmentally regulated. In addition, the expression is regulated in a copy-dependent manner irrespective of where the transgene is integrated, suggesting that a mechanism excluding the effect of the integration site exists within the transgene itself. To explore the conformational change of this gene in the genome, the DNase I hypersensitive sites of the gene were examined. Three sites (DHS-1,2, and 3) were identified upstream and downstream of the gene and these sites were retained in the transgene as well as in the gene observed endogenously.

Animals↗
PubMed2000

Targeted localized degradation of Paired protein in Drosophila development.

BACKGROUND: Selective spatial regulation of gene expression lies at the core of pattern formation in the embryo. In the fruit fly Drosophila, localized transcriptional regulation accounts for much of the embryonic pattern. RESULTS: We identified a gene, partner of paired (ppa), whose properties suggest that localized receptors for protein degradation are integrated into regulatory networks of transcription factors to ensure robust spatial regulation of gene expression. We found that the Ppa protein interacts with the Pax transcription factor Paired (Prd) and contains an F-box, a motif found in receptors for ubiquitin-mediated protein degradation. In normal development, Prd functions only in cells in which ppa mRNA expression has been repressed by another segmentation protein, Even-skipped (Eve). When ppa was expressed ectopically in these cells, Prd protein, but not mRNA, levels diminished. When ppa function was removed from cells that express prd mRNA, Prd protein levels increased. CONCLUSIONS: Ppa co-ordinates Prd degradation and is important for expression of Prd to be correctly localized. In the presence of Ppa, Prd protein is targeted for degradation at sites where its mis-expression would disrupt development. In the absence of Ppa, Prd is longer-lived and regulates downstream target genes.

Amino Acid Sequence↗
PubMedDate not supplied

Independence of fushi tarazu expression with respect to cellular density in Drosophila embryos.

Regularly spaced repeated morphological structures are a common developmental theme among higher eukaryotes. In Drosophila, this is evident in the repeated segments of the larval and the adult cuticle. It has been demonstrated through cell transplantation and more recently through molecular techniques that these repeated segmental units are established as early as nuclear cycle 14 in the blastoderm embryo. A number of genes have been shown to express their transcripts, and in two instances their protein products, in a spatially restricted manner at this early stage. Immunofluorescence probes against the protein product of one such gene, fushi tarazu (ftz), reveal that it is distributed in seven evenly spaced stripes across the cellularized cycle-14 blastoderm embryo. The mechanisms that determine such spatial patterns of gene expression are of fundamental importance for the development of multicellular organisms, but in no case are they well understood. Here we examine the ftz pattern on blastoderm embryos derived from maternal-haploid 1182 (mh 1182) and daughterless-abo-like (dal) females which possess cell densities and sizes both above and below the wild-type levels. The number, spacing and width of the ftz protein positive bands are not altered in these abnormal embryos relative to the wild-type pattern, suggesting that the mechanism by which distance is measured with respect to the ftz protein is independent of cell size and density.

Animals↗
PubMed1998

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: transgenic rescue and interactions with gene background.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an approximately 50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKCepsilon expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKCepsilon expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.

Animals↗
PubMed1998

Dissecting embryonic and seedling morphogenesis in Arabidopsis by promoter trap insertional mutagenesis.

Development can be considered to comprise the co-ordinated regulation of patterning at different levels: patterning of cells to form tissues, patterning of tissues to form organs, and patterning of organs to generate the characteristic architecture of the organism. These processes are expected, in turn, to be mediated by the precise spatial and temporal regulation of patterns of gene expression during development, which depend on appropriate signalling mechanisms. In order to investigate molecular events of morphogenesis in plants, we have utilized a system of promoter trap insertional mutagenesis in Arabidopsis, to generate both phenotypic mutants and gene fusions that represent markers useful in studying the regulation of patterning. A screen of transgenic seedlings containing a T-DNA promoter trap has led to the identification of mutants defective in seedling shape and embryonic development, and of GUS fusion genes that are expressed in spatially restricted patterns. Mutants have been crossed with marker lines expressing cell type-specific GUS activities, to investigate their cellular organization. For example, the POLARIS marker gene is expressed in the embryonic and seedling root tip. When crossed with hydra, which lacks an embryonic root, and with emb30, which lacks both embryonic and seedling roots, it is nevertheless expressed in the correct relative position, and we hypothesize that it represents a novel marker of root positional information, independent of root morphogenesis.

Arabidopsis↗
PubMed2001

Bep4 protein is involved in patterning along the animal-vegetal axis in the Paracentrotus lividus embryo.

In sea urchin embryos, the initial animal-vegetal (AV) axis is specified during oogenesis but the mechanism is largely unknown. By using chemical reagents such as lithium, it is possible to shift the principal embryonic territories toward a vegetal fate. We have investigated the possibility of obtaining the same morphological effect as with lithium by utilizing Fabs against the maternal Bep4 protein that is localized in the animal part of Paracentrotus lividus egg and embryos. Incubation of fertilized eggs with Fabs against Bep4 protein causes exogastrulation at 48 h of development of P. lividus embryos, similar to embryos treated with lithium. This vegetalizing effect was ascertained by utilizing territorial markers such as EctoV, EndoI, and Ig8. The effect of Fabs against Bep4 on gene expression was observed by monitoring spatial expression of the hatching enzyme gene. A decreased expression domain compared to its normal spatial distribution was detected and this effect was again comparable to those obtained with lithium treatment. Association of Bep4 with a cadherin was demonstrated by immunoprecipitation and immunostaining experiments, and an involvement in cell signaling is discussed. In addition, treatment of embryos with anti-Bep4 Fabs causes an enhancement in the level and an expansion in the pattern of nuclear beta-catenin. Moreover, this treatment also provokes a decrease of beta-catenin in adherens junctions. Together, these data indicate that anti-Bep4 Fabs provoke a shift of the animal-vegetal boundary toward the animal pole and suggest an active role of Bep4 protein in patterning along the AV axis.

Adherens Junctions↗
PubMed2002

Spatial repression of PCNA by p53 during kidney development.

Transcriptional repression is a key mechanism for the spatial specification of gene expression and cell fate determination. During kidney development, proliferating cell nuclear antigen (PCNA) is expressed in the nephrogenic zone and is downregulated rapidly as renal epithelial cells enter terminal differentiation and acquire functional characteristics. Our laboratory reported that the transcription factor p53 stimulates the terminal differentiation of renal epithelial cells by means of transcriptional activation of renal function genes (Saifudeen Z, Dipp S, and El-Dahr SS. J Clin Invest 109: 1021-1030, 2002). Because p53-induced growth arrest correlates with downregulation of PCNA gene expression, we examined the impact of p53 inactivation on PCNA expression in mice and evaluated the effect of p53 on PCNA transcription. Immunohistochemistry revealed that the transition from nephrogenesis to terminal epithelial cell differentiation correlates with accumulation of the transcription factor p53. Importantly, the spatially restricted pattern of PCNA expression is disrupted in kidneys of p53-deficient pups, in which there was a redistribution of PCNA expression into the differentiation zone (without a change in total kidney PCNA content) and distortion of the tubular architecture. Electrophoretic mobility shift assays revealed that the binding of kidney nuclear extracts to the p53 response elements in human and rat PCNA promoters is developmentally regulated. Transient transfection assays performed in p53-deficient HeLa cells revealed that exogenous p53 strongly represses transcription from human PCNA promoter-reporter constructs. Interestingly, deletion of the p53-binding site confers enhanced responsiveness to p53-mediated repression, suggesting that transcriptional repression of PCNA by p53 is achieved by a mechanism other than direct DNA binding. On the basis of these results, we propose the hypothesis that p53-mediated transcriptional repression plays a role in the spatial restriction of PCNA gene expression during normal renal development.

Amino Acid Sequence↗
PubMed1999

Spatial and temporal changes in myosin heavy chain gene expression in skeletal muscle development.

Seven myosin heavy chains (MyHC) are expressed in mammalian skeletal muscle in spatially and temporally regulated patterns. The timing, distribution, and quantitation of MyHC expression during development and early postnatal life of the mouse are reported here. The three adult fast MyHC RNAs (IIa, IIb, and IId/x) are expressed in the mouse embryo and each mRNA has a distinct temporal and spatial distribution. In situ hybridization analysis demonstrates expression of IIb mRNA by 14.5 dpc, which proceeds developmentally in a rostral to caudal pattern. IId/x and IIa mRNAs are detectable 2 days later. Ribonuclease protection assays demonstrate that the three adult fast genes are expressed at approximately equal levels relative to each other in the embryo but at quite low levels relative to the two developmental isoforms, embryonic and perinatal. Just after birth major changes in the relative proportions of different MyHC RNAs and protein occur. In all cases, RNA expression and protein expression appear coincident. The changes in MyHC RNA and protein expression are distinct in different muscles and are restricted in some cases to particular regions of the muscle and do not always reflect their distribution in the adult.

Animals↗