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At least 1,495 records · Page 83Linked to original sources
PubMed2006

Genome-wide survey of imprinted genes.

The developmental failure of mammalian parthenogenote has been a mystery for a long time and posed a question as to why bi-parental reproduction is necessary for development to term. In the 1980s, it was proven that this failure was not due to the genetic information itself, but to epigenetic modification of genomic DNA. In the following decade, several studies successfully identified imprinted genes which were differentially expressed in a parent-of-origin-specific manner, and it was shown that the differential expression depended on the pattern of DNA methylation. These facts prompted development of genome-wide systematic screening methods based on DNA methylation and differential gene expression to identify imprinted genes. Recently computational approaches and microarray technology have been introduced to identify imprinted genes/loci, contributing to the expansion of our knowledge. However, it has been shown that the gene silencing derived from genomic imprinting is accomplished by several mechanisms in addition to direct DNA methylation, indicating that novel approaches are further required for comprehensive understanding of genomic imprinting. To unveil the mechanism of developmental failure in mammalian parthenogenote, systematic screenings for imprinted genes/loci have been developed. In this review, we describe genomic imprinting focusing on the history of genome-wide screening.

Animals↗
PubMed1994

The beetle Tribolium castaneum has a fushi tarazu homolog expressed in stripes during segmentation.

The genetic control of embryonic organization is far better understood for the fruit fly Drosophila melanogaster than for any other metazoan. A gene hierarchy acts during oogenesis and embryogenesis to regulate the establishment of segmentation along the anterior-posterior axis, and homeotic selector genes define developmental commitments within each parasegmental unit delineated. One of the most intensively studied Drosophila segmentation genes is fushi tarazu (ftz), a pair-rule gene expressed in stripes that is important for the establishment of the parasegmental boundaries. Although ftz is flanked by homeotic selector genes conserved throughout the metazoa, there is no evidence that it was part of the ancestral homeotic complex, and it has been unclear when the gene arose and acquired a role in segmentation. We show here that the beetle Tribolium castaneum has a ftz homolog located in its Homeotic complex and expressed in a pair-rule fashion, albeit in a register differing from that of the fly gene. These and other observations demonstrate that a ftz gene preexisted the radiation of holometabolous insects and suggest that it has a role in beetle embryogenesis which differs somewhat from that described in flies.

Amino Acid Sequence↗
PubMed2005

Polyamines are involved in murine kidney development controlling expression of c-ret, E-cadherin, and Pax2/8 genes.

Polyamines play an important role in cell growth and differentiation. We studied changes in morphogenesis and the expression of the developmental control genes in the embryonic mouse kidney in response to polyamine depletion, using a kidney organ culture approach and reducing the polyamine pools with alpha-difluoromethylornithine (DFMO), an irreversible suicide inhibitor of ornithine decarboxylase (ODC). We found that inhibition of ODC results in a systematic kidney organogenesis phenotype, in that the DFMO-treated kidney specimens were of smaller size, had less epithelial ureteric bud branches, and their mesenchymal-derived tubule formation was retarded. These dysmorphologies were shown to be associated with changes in cell proliferation. Whole-mount in situ experiments revealed that inhibition of ODC causes increases in epithelial c-ret and E-cadherin and a decrease in mesenchymal Pax-8 expression, whereas levels of epithelial Wnt-11, mesenchymal GDNF, FoxD1, and Pax-2 transcripts remain unchanged. We studied regulation of the Pax-2 gene by analyzing a mouse line in which lacZ was driven by an 8.5 kb Pax-2 enhancer in the epithelial ureteric bud, and found that Pax-2 expression, as indicated by lacZ expression, increased after DFMO treatment. Transient transfection experiments in HEK 293 cells with the minimal Pax-2 promoter showed enhanced transcription upon reduction of the polyamine pools. We propose that ODC and polyamines have an important role in kidney organogenesis, being involved in the regulation of the expression of genes implicated in epithelial-mesenchymal tissue interactions.

Animals↗
PubMed1998

Alzheimer's disease and brain development: common molecular pathways.

Research on the causes and treatments of Alzheimer's disease (AD) has led investigators down numerous avenues. Although many models have been proposed, no single model of AD satisfactorily accounts for all neuropathologic findings as well as the requirement of aging for disease onset. The mechanisms of disease progression are equally unclear. We hypothesize that alternative gene expression during AD plays a critical role in disease progression. Numerous developmentally regulated genes and cell cycle proteins have been shown to be re-expressed or activated during AD. These proteins include transcription factors, members of the cell cycle regulatory machinery, and programmed cell death genes. Such proteins play an important role during brain development and would likely exert powerful effects if re-expressed in the adult brain. We propose that the re-expression or activation of developmentally regulated genes define molecular mechanisms active both during brain development and in AD.

Alzheimer Disease↗
PubMed2004

Sexual and temporal dynamics of molecular evolution in C. elegans development.

Dissection of the phenotypic and molecular details of development and differentiation is a centuries-old topic in evolutionary biology. However, an adequate understanding is missing for the molecular evolution of genes that are expressed differentially throughout development-across time, tissues, and the sexes. In this study, we investigate the dynamics of gene evolution across Caenorhabditis elegans ontogeny and among genes expressed differentially between each sex and gamete type. Using gene classes identified by genome-wide gene expression developmental time series and comparative sequence analysis with the congener C. briggsae, we demonstrate that genes expressed predominantly after reproductive maturity evolve more rapidly than genes expressed earlier in development and that genes expressed transiently during embryogenesis evolve faster than other embryonic transcripts. These results are indicative of relaxed selection on genes expressed after maturity, in accord with the mutation-accumulation model of aging. Furthermore, genes involved in spermatogenesis reveal more rapid evolution than other phenotypic classes of genes. Average rates of evolution among male soma-related genes indicates that selection acts to maintain males in these androdioecious species, despite their rarity, and the rapid evolution of sperm genes suggests that sexual selection acts on sperm development and function.

Aging↗
PubMed1993

Direct induction of DNA hypermethylation in sea urchin embryos by microinjection of 5-methyl dCTP stimulates early histone gene expression and leads to developmental arrest.

The role of DNA methylation in gene inactivation has been studied extensively in vertebrates but it is not clear whether it serves similar functions in other organisms. We devised a novel approach to induce hypermethylation of both endogenous and injected DNA in the sea urchin Lytechinus pictus in order to study the effect of DNA methylation on gene expression in this invertebrate. By injecting 5-methyl dCTP either alone or together with a cloned DNA construct into fertilized sea urchin eggs, replicating DNA became hypermethylated from the random incorporation of the methylated nucleotide in place of cytosine during DNA synthesis. During subsequent rounds of replication, the injected 5-methyl dCTP became depleted but methylation at CpG sites was still elevated presumably due to the action of a methyltransferase enzyme. Using this approach, we studied the effect of hypermethylation on two members of the sea urchin multigene family, the early H2B and the late H2B genes. De novo methylation was shown to occur at known cis-regulatory regions of the genes. The effect of methylation on gene activity was probed using RNase protection assay. Methylation resulted in increased early H2B histone gene expression but had no effect on late H2B histone gene expression. These results demonstrate that methylation does not necessarily inactivate genes in the sea urchins as previously thought. Interestingly, the development of embryos injected with 5-methyl dCTP typically was arrested at the blastula stage, and analysis of the genomic DNA extracted from injected embryos showed a significant increase in the endogenous methylation content. These data suggest that perturbation of methylation patterns in developmental sea urchin embryos may be responsible for the developmental arrest through altering the gene expression pattern.

Animals↗
PubMed1995

Conservation of Brachyury (T) genes in amphioxus and vertebrates: developmental and evolutionary implications.

Homologues of the murine Brachyury (T) gene have been cloned from several vertebrates, and are implicated in mesoderm formation and in differentiation of the notochord. In contrast, the roles of the ascidian Brachyury gene may be restricted to presumptive notochord. To understand the evolution of Brachyury genes and their developmental roles, we have searched for homologues in amphioxus, representing the third chordate subphylum and the probable closest relative of the vertebrates. We report the isolation of two amphioxus cDNA clones with clear homology to Brachyury genes, and demonstrate that these derive from separate loci resultant from a recent gene duplication. This finding represents an exception to the emerging consensus of an archetypal prevertebrate genome in amphioxus. The spatial and temporal distribution of Brachyury transcripts during amphioxus development is remarkably similar to vertebrate Brachyury, in presumptive mesoderm, posterior mesoderm and the notochord. Gene expression extends throughout the anteroposterior axis of the notochord, despite the most rostral regions being a more recent specialization; it also persists into larval stages, despite differentiation into contractile tissue. We propose that roles of Brachyury in notochord differentiation are more ancient than roles in mesoderm formation, and that the latter are shared by cephalochordates and all vertebrates.

Animals↗
PubMed2007

Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung.

Developmentally important genes have recently been linked to tissue regeneration and epithelial cell repair in neonatal and adult animals in several organs, including liver, skin, prostate, and musculature. We hypothesized that developmentally important genes play roles in lung injury repair in adult mice. Although there is considerable information known about these processes, the specific molecular pathways that mediate injury and regulate tissue repair are not fully elucidated. Using a hyperoxic injury model to study these mechanisms of lung injury and tissue repair, we selected the following genes based upon their known or putative roles in lung development and organogenesis: TTF-1, FGF9, FGF10, BMP4, PDGF-A, VEGF, Ptc, Shh, Sca-1, BCRP, CD45, and Cyclin-D2. Our findings demonstrate that several developmentally important genes (Sca-1, Shh, PDGF-A, VEGF, BCRP, CD45, BMP4, and Cyclin-D2) change during hyperoxic injury and normoxic recovery in mice, suggesting that adult lung may reactivate key developmental regulatory pathways for tissue repair. The mRNA for one gene (TTF-1), unchanged during hyperoxia, was upregulated late in recovery phase. These novel findings provide the basis for testing the efficacy of post-injury lung repair in animals genetically modified to inactivate or express individual molecules.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse.

BACKGROUND: Developmentally important genes often result in early lethality in knockout animals. Thus, the direct role of genes in late gestation organogenesis cannot be assessed directly. In utero delivery of transgenes was shown previously to result in high efficiency transfer to pulmonary and intestinal epithelial stem cells. Thus, this technology can be used to evaluate late gestation development. RESULTS: In utero gene transfer was used to transfer adenovirus with either an antisense c-myc or a C-MYC ubiquitin targeting protein to knockout out c-myc expression in late gestation lung and intestines. Using either antisense or ubiquitin mediated knockout of C-MYC levels in late gestation resulted in similar effects. Decreased complexity was observed in both intestines and lungs. Stunted growth of villi was evident in the intestines. In the lung, hypoplastic lungs with disrupted aveolarization were observed. CONCLUSIONS: These data demonstrated that C-MYC was required for cell expansion and complexity in late gestation lung and intestinal development. In addition they demonstrate that transient in utero knockout of proteins may be used to determine the role of developmentally important genes in the lungs and intestines.

Adenoviridae↗
PubMed1992

A Xenopus homologue of the human beta-amyloid precursor protein: developmental regulation of its gene expression.

Complimentary DNA clones have been isolated from Xenopus larva to delineate a protein highly homologous to the human beta-amyloid precursor protein (APP). Developmental change of Xenopus APP gene expression has been analyzed with molecular probes. From early oogenesis, there is a high accumulation of maternal APP. After fertilization, the mRNA is degraded, reaching a minimum level around the gastrula stage. Then zygotic transcription appears to be initiated, and this continues during the subsequent embryonic and larval stages. Splicing patterns differ between the maternal and zygotic transcripts. The ratio of mRNA including the protease inhibitor domain (PID) sequence is extremely low for the transcript of maternal origin as compared to that for the transcript of zygotic origin. These results suggest some roles for the APP molecule in Xenopus early development.

Amino Acid Sequence↗
PubMed2003

The ethanol switch: a tool for tissue-specific gene induction during plant development.

Controlled gene expression in time and space is a powerful tool for the analysis of gene function during plant development. Here, we report ethanol inducible gene expression in defined sub-domains of the shoot apical and floral meristems. For this, expression of an ethanol-regulated transcription factor, ALCR, is restricted to precise domains using specific promoters. Gene expression activation is followed using reporters under the control of the alcA promoter, which responds to ALCR only in the presence of the ethanol. We demonstrate that precise control of spatially limited gene expression can be achieved. The kinetics of reporter gene activation and inactivation following a pulse of ethanol induction shows that the system is dynamic and suitable for precise temporal control of expression. The system is both flexible and robust, permitting simultaneous expression of two genes in a given domain or, conversely, the expression of a gene in two separate domains. We also show that this strategy can be applied to mis-express genes with developmental roles, by manipulating expression of the SHOOT MERISTEMLESS (STM) and CYCLIN D3;1 (CYCD3;1) genes during plant development.

Arabidopsis↗
PubMed1997

A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with Rh3 in R7 cells.

The photoreceptor cells of the Drosophila compound eye are precisely organized in elementary units called ommatidia. The outer (R1-R6) and inner (R7, R8) photoreceptors represent two physiologically distinct systems with two different projection targets in the brain (for review see Hardie, 1985). All cells of the primary system, R1-R6, express the same rhodopsin and are functionally identical. In contrast, the R7 and R8 photoreceptors are different from each other. They occupy anatomically precise positions, with R7 on top of R8. In fact, there are several classes of R7/R8 pairs, which differ morphologically and functionally and are characterized by the expression of one of two R7-specific opsins, rh3 or rh4. Here, we describe the identification of a new opsin gene, rhodopsin 5, expressed in one subclass of R8 cells. Interestingly, this subclass represents R8 cells that are directly underneath the R7 photoreceptors expressing rh3, but are never under those expressing rh4. These results confirm the existence of two subpopulations of R7 and R8 cells, which coordinate the expression of their respective rh genes. Thus, developmental signaling pathways between R7 and R8 lead to the exclusive expression of a single rhodopsin gene per cell and to the coordinate expression of another one in the neighboring cell. Consistent with this, rh5 expression in R8 disappears when R7 cells are absent (in sevenless mutant). We propose a model for the concerted evolution of opsin genes and the elaboration of the architecture of the retina.

Amino Acid Sequence↗
PubMed1992

A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.

We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.

Amino Acid Sequence↗
PubMed2026

Cultivar-dependent regulation of cytokinin biosynthesis in wheat: developmental expression of TaIPT genes and hormonal crosstalk during reproductive development.

BACKGROUND: Cytokinins are key regulators of plant growth, reproductive development, and yield formation. In cereals, cytokinin biosynthesis is catalyzed by isopentenyltransferase (IPT) enzymes, yet the genomic organization and developmental regulation of IPT genes in polyploid wheat remain incompletely understood, especially at the cultivar level. RESULTS: Here, we present an integrated genomic, transcriptional, and hormonal analysis of the TaIPT gene family during vegetative and reproductive development in two wheat cultivars, awnless Kontesa and awned Ostka. Genome-wide analysis identified nine core TaIPT genes represented by 25 homoeologs distributed across the A, B, and D subgenomes, for which a unified nomenclature was established. Phylogenetic analysis resolved TaIPTs into conserved evolutionary clades corresponding to ATP/ADP-dependent and tRNA-dependent IPT groups. Expression profiling revealed distinct spatial and temporal patterns of TaIPT transcription across roots, leaves, inflorescences, and developing spikes. Several TaIPT genes showed enhanced expression during early reproductive stages, coinciding with dynamic changes in cytokinin concentrations. Comparative analyses revealed cultivar-specific expression and co-variation patterns, with Kontesa displaying more compartmentalized TaIPT expression and Ostka showing coordinated activation of multiple TaIPT genes during early grain development. Hormone profiling further indicated stage-dependent associations between TaIPT expression, cytokinin metabolism, and the balance between cytokinins and abscisic acid. These relationships are interpreted as correlative and provide a framework for future functional testing rather than direct evidence of causality. CONCLUSIONS: Together, these results provide a cultivar-focused framework for understanding the organization and regulation of cytokinin biosynthesis genes in wheat. The data highlight cultivar-dependent TaIPT expression patterns and their association with cytokinin dynamics during reproductive development, while also identifying the need for homoeolog-specific and functional validation. This study establishes a foundation for future research on cytokinin-mediated regulation of wheat growth and grain development.

Triticum↗
PubMed1992

The multiple beta-tubulin genes of Xenopus: isolation and developmental expression of a germ-cell isotype beta-tubulin gene.

In this report, we demonstrate the presence of multiple beta-tubulin genes in Xenopus and begin to explore the regulation of isotypes within the beta-tubulin family by focusing on the characterization of a specific beta-tubulin cDNA derived from a Xenopus oocyte library. This clone (XLOT: Xenopus laevis oocyte beta-tubulin) contains the entire protein coding and 3'-untranslated regions of the gene, and is only missing approximately eleven nucleotides from the start of transcription. The XLOT transcript is ubiquitously expressed, but steady-state amounts are highest in immature oocytes and in testes. Consistent with the present understanding of this type of autoregulation, levels of oocyte beta-tubulin transcript vary in accordance with fluctuating polymeric/monomeric tubulin protein ratios both in the developing oocyte and as the late stage oocyte matures to an unfertilized egg. In addition, steady-state levels of the oocyte beta-tubulin transcript do not increase as the total number of cells per embryo increase during embryogenesis. Although one major and three minor transcriptional start sites are utilized in immature oocytes and adult tissues, usage of each individual site varies during oogenesis and embryogenesis. The preferential expression in germ cells indicate that the oocyte beta-tubulin transcript may provide a useful marker for gonadal differentiation in early amphibian development.

Amino Acid Sequence↗
PubMed1995

Cloning of the promoter-regulatory region of the murine growth hormone receptor gene. Identification of a developmentally regulated enhancer element.

The growth hormone (GH) receptor is essential for the actions of GH on postnatal growth and metabolism. To identify DNA sequences involved in the regulation of transcription of the murine GH receptor gene, a 17-kilobase genomic clone containing the 5'-flanking region, exon 1, and part of intron 1 of the murine GH receptor gene was isolated. Utilizing primer extension and ribonuclease protection assays, two major transcription start sites were identified in RNA from liver of male, female, and pregnant mice. Transient transfection studies using a reporter gene demonstrated promoter activity in a variety of eukaryotic cells. Deletional analysis and DNA-protein binding assays led to the identification of a 30-base pair enhancer element located about 3.4 kilobases upstream of the transcription start sites. Computer analysis of the nucleotide sequence of the enhancer element did not reveal any potential DNA binding motifs for known transcription factors, and this DNA element failed to exhibit binding activity for some common transcription factors. Analysis of both functional activity and DNA-protein binding activity of this enhancer element in adult and fetal hepatocytes suggests that this DNA element may play a role in the developmental expression of the GH receptor gene.

Animals↗
PubMed1996

The paired-box transcription factor, PAX2, positively modulates expression of the Wilms' tumor suppressor gene (WT1).

The Wilms' tumor suppressor gene, wt1, encodes a zinc finger protein which functions as a transcriptional regulator. Expression of the wt1 gene is developmentally regulated and restricted to a small set of tissues which include the fetal urogenital system, mesothelium, and spleen. In the developing kidney, induction of neprohogenesis by the ureter is accompanied by an increase in expression levels of the Pax-2 gene, a developmentally and spatially regulated paired-box member. This is followed by an increase in wt1 expression as mesenchymal cells condense and differentiate. In this report, we demonstrate that PAX2 isoforms are capable of transactivating the wt1 promoter. Deletion mutagenesis of the wt1 promoter identified an element responsible for mediating PAX2 responsiveness, located between nucleotides -33 and -71 relative to the first wt1 transcription start site. Consistent with its identity as a PAX responsive element, multimerization of this mofit upstream of a heterologous minimal promoter enhanced reporter activity when co-transfected with a Pax-2 expression vector. Finally, we demonstrate that PAX2 can stimulate expression of the endogenous wt1 gene. These results suggest that a role for PAX2 during mesenchyme-to-epithelium transition in renal development is to induce wt1 expression.

3T3 Cells↗
PubMed1998

Sequence and expression of a novel mouse gene PRDC (protein related to DAN and cerberus) identified by a gene trap approach.

Gene trapping in embryonic stem (ES) cells was used to identify a novel gene involved in mouse development. In order to screen trapped ES cell lines for the presence of developmentally regulated genes, an in vitro differentiation test was used. One of the G418 resistant cell lines, in conjunction with the lacZ reporter gene, showed differential expression patterns under differentiated and undifferentiated conditions. The gene trap insertion in this cell line was germ-line transmitted and X-gal staining was used to assess the expression pattern of lacZ in embryos heterozygous for the trapped allele. The reporter gene's expression was detected in commissural neurons in the developing spinal cord, suggesting functions for the trapped gene in mouse neural development. Structural analysis of the cDNA revealed that this trapped gene, named PRDC (protein related to DAN and cerberus), is a novel gene that encodes a putative secretory protein consisting of 168 amino acid residues. PRDC gene product shows limited similarities to the products of DAN (differential screening-selected gene aberrative in neuroblastoma) and cerberus. (DAN is a possible tumor-suppressor for neuroblastoma in human. Cerberus can induce an ectopic head in Xenopus embryos when ectopically expressed.) These three gene products may form a novel family of signaling molecules.

Alleles↗